Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases
Weng, Q. et al. Global burden of early-onset osteoarthritis, 1990–2019: results from the Global Burden of Disease Study 2019. Ann. Rheum. Dis. 83, 915–925 (2024).
Sebbag, E. et al. The worldwide burden of musculoskeletal diseases: a systematic analysis of the World Health Organization burden of diseases database. Ann. Rheum. Dis. 78, 844–848 (2019).
Google Scholar
Fu, W. et al. Na(v)1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis. Nature 625, 557–565 (2024).
Google Scholar
Qin, L. et al. Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues. Bone Res. 9, 44 (2021).
Google Scholar
Wu, X. et al. Kindlin-2 preserves integrity of the articular cartilage to protect against osteoarthritis. Nat. Aging 2, 332–347 (2022).
Google Scholar
Tang, W. et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 332, 478–484 (2011).
Google Scholar
Glyn-Jones, S. et al. Osteoarthritis. Lancet 386, 376–387 (2015).
Google Scholar
Moore, B. W. & Perez, V. J. Specific acidic proteins of the nervous system. Osteoarthritis and Cartilage/OARS, Osteoarthritis Research Society ed. F. D. Carlson, 343–359 (Prentice-Hall, 1967).
Aitken, A. 14-3-3 proteins: a historic overview. Semin. Cancer Biol. 16, 162–172 (2006).
Google Scholar
Gardino, A. K., Smerdon, S. J. & Yaffe, M. B. Structural determinants of 14-3-3 binding specificities and regulation of subcellular localization of 14-3-3-ligand complexes: a comparison of the X-ray crystal structures of all human 14-3-3 isoforms. Semin. Cancer Biol. 16, 173–182 (2006).
Google Scholar
Cau, Y., Valensin, D., Mori, M., Draghi, S. & Botta, M. Structure, function, involvement in diseases and targeting of 14-3-3 proteins: an update. Curr. Med. Chem. 25, 5–21 (2018).
Google Scholar
Celis, J. E. et al. Comprehensive two-dimensional gel protein databases offer a global approach to the analysis of human cells: the transformed amnion cells (AMA) master database and its link to genome DNA sequence data. Electrophoresis 11, 989–1071 (1990).
Google Scholar
Fu, H., Subramanian, R. R. & Masters, S. C. 14-3-3 proteins: structure, function, and regulation. Annu. Rev. Pharmacol. Toxicol. 40, 617–647 (2000).
Google Scholar
Skoulakis, E. M. & Davis, R. L. 14-3-3 proteins in neuronal development and function. Mol. Neurobiol. 16, 269–284 (1998).
Google Scholar
Jia, Y. et al. Targeting macrophage TFEB-14-3-3 epsilon Interface by naringenin inhibits abdominal aortic aneurysm. Cell Discov. 8, 21 (2022).
Google Scholar
Zhang, Y. et al. 14-3-3epsilon: a protein with complex physiology function but promising therapeutic potential in cancer. Cell Commun. Signal. 22, 72 (2024).
Google Scholar
Yaffe, M. B. et al. The structural basis for 14-3-3:phosphopeptide binding specificity. Cell 91, 961–971 (1997).
Google Scholar
Obsilova, V. & Obsil, T. Structural insights into the functional roles of 14-3-3 proteins. Front. Mol. Biosci. 9, 1016071 (2022).
Google Scholar
Low, Z. Y., Yip, A. J. W., Chan, A. M. L. & Choo, W. S. 14-3-3 family of proteins: biological implications, molecular interactions, and potential intervention in cancer, virus, and neurodegeneration disorders. J. Cell. Biochem. 125, e30624 (2024).
Google Scholar
Stevers, L. M. et al. Modulators of 14-3-3 protein-protein interactions. J. Med. Chem. 61, 3755–3778 (2018).
Google Scholar
Sluchanko, N. N. & Bustos, D. M. Intrinsic disorder associated with 14-3-3 proteins and their partners. Prog. Mol. Biol. Transl. Sci. 166, 19–61 (2019).
Google Scholar
Rivero, G. et al. 14-3-3epsilon protein-immobilized PCL-HA electrospun scaffolds with enhanced osteogenicity. J. Mater. Sci. Mater. Med. 30, 99 (2019).
Google Scholar
Kim, H. et al. Selenoprotein W ensures physiological bone remodeling by preventing hyperactivity of osteoclasts. Nat. Commun. 12, 2258 (2021).
Google Scholar
Yoon, H. E., Kim, K. S. & Kim, I. Y. 14-3-3 eta inhibits chondrogenic differentiation of ATDC5 cell. Biochem. Biophys. Res. Commun. 406, 59–63 (2011).
Google Scholar
Tazawa, H., Takahashi, S. & Zilliacus, J. Interaction of the parathyroid hormone receptor with the 14-3-3 protein. Biochim. Biophys. Acta 1620, 32–38 (2003).
Google Scholar
Fu, W. et al. TNFR2/14-3-3epsilon signaling complex instructs macrophage plasticity in inflammation and autoimmunity. J. Clin. Investig. 131, e144016 (2021).
Wu, Q., Zhu, J., Liu, F., Liu, J. & Li, M. Downregulation of 14-3-3beta inhibits proliferation and migration in osteosarcoma cells. Mol. Med. Rep. 17, 2493–2500 (2018).
Google Scholar
Gong, X. et al. Elevated serum 14-3-3eta protein may be helpful for diagnosis of early rheumatoid arthritis associated with secondary osteoporosis in Chinese population. Clin. Rheumatol. 36, 2581–2587 (2017).
Google Scholar
Fu, W. et al. 14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis. Ann. Rheum. Dis. 80, 1615–1627 (2021).
Google Scholar
Millerand, M. et al. Activation of innate immunity by 14-3-3 epsilon, a new potential alarmin in osteoarthritis. Osteoarthr. Cartil. 28, 646–657 (2020).
Google Scholar
Trimova, G. et al. Tumour necrosis factor-alpha promotes secretion of 14-3-3eta by inducing necroptosis in macrophages. Arthritis Res. Ther. 22, 24 (2020).
Google Scholar
Yang, X. et al. Structural basis for protein-protein interactions in the 14-3-3 protein family. Proc. Natl. Acad. Sci. USA 103, 17237–17242 (2006).
Google Scholar
Obsil, T. & Obsilova, V. Structural basis of 14-3-3 protein functions. Semin. Cell Dev. Biol. 22, 663–672 (2011).
Google Scholar
Halskau, O. Jr. et al. Three-way interaction between 14-3-3 proteins, the N-terminal region of tyrosine hydroxylase, and negatively charged membranes. J. Biol. Chem. 284, 32758–32769 (2009).
Google Scholar
Abdi, G. et al. 14-3-3 proteins-a moonlight protein complex with therapeutic potential in neurological disorder: in-depth review with Alzheimer’s disease. Front. Mol. Biosci. 11, 1286536 (2024).
Google Scholar
Darling, D. L., Yingling, J. & Wynshaw-Boris, A. Role of 14-3-3 proteins in eukaryotic signaling and development. Curr. Top. Dev. Biol. 68, 281–315 (2005).
Google Scholar
Munier, C. C., Ottmann, C. & Perry, M. W. D. 14-3-3 modulation of the inflammatory response. Pharmacol. Res. 163, 105236 (2021).
Google Scholar
Muslin, A. J., Tanner, J. W., Allen, P. M. & Shaw, A. S. Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. Cell 84, 889–897 (1996).
Google Scholar
Mann, J. et al. Non-canonical BAD activity regulates breast cancer cell and tumor growth via 14-3-3 binding and mitochondrial metabolism. Oncogene 38, 3325–3339 (2019).
Google Scholar
Sadik, G. et al. Phosphorylation of tau at Ser214 mediates its interaction with 14-3-3 protein: implications for the mechanism of tau aggregation. J. Neurochem.108, 33–43 (2009).
Google Scholar
Obsilova, V. & Obsil, T. The 14-3-3 Proteins as important allosteric regulators of protein kinases. Int. J. Mol. Sci. 21, 8824 (2020).
Kongsamut, S. & Eishingdrelo, H. Modulating GPCR and 14-3-3 protein interactions: prospects for CNS drug discovery. Drug Discov. Today 28, 103641 (2023).
Google Scholar
Eishingdrelo, H., Qin, X., Yuan, L., Kongsamut, S. & Yu, L. Ligands can differentially and temporally modulate GPCR interaction with 14-3-3 isoforms. Curr. Res. Pharmacol. Drug Discov. 3, 100123 (2022).
Google Scholar
Ferl, R. J., Manak, M. S. & Reyes, M. F. The 14-3-3s. Genome Biol. 3, REVIEWS3010 (2002).
Google Scholar
Vigneswara, V. & Ahmed, Z. The role of caspase-2 in regulating cell fate. Cells 9, 1259 (2020).
Ramakrishnan, G. et al. AKT and 14-3-3 regulate Notch4 nuclear localization. Sci. Rep. 5, 8782 (2015).
Google Scholar
Seif, F. et al. The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun. Signal 15, 23 (2017).
Google Scholar
Villarino, A. V., Kanno, Y. & O’Shea, J. J. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat. Immunol. 18, 374–384 (2017).
Google Scholar
Kacirova, M., Novacek, J., Man, P., Obsilova, V. & Obsil, T. Structural Basis for the 14-3-3 protein-dependent inhibition of phosducin function. Biophys. J. 112, 1339–1349 (2017).
Google Scholar
Agarwal-Mawal, A. et al. 14-3-3 connects glycogen synthase kinase-3 beta to tau within a brain microtubule-associated tau phosphorylation complex. J. Biol. Chem. 278, 12722–12728 (2003).
Google Scholar
Huang, X. et al. 14-3-3 proteins are potential regulators of liquid-liquid phase separation. Cell Biochem. Biophys. 80, 277–293 (2022).
Google Scholar
Masters, S. C. et al. Survival-promoting functions of 14-3-3 proteins. Biochem. Soc. Trans. 30, 360–365 (2002).
Google Scholar
Liu, J. et al. The role of 14-3-3 proteins in cell signalling pathways and virus infection. J. Cell Mol. Med. 25, 4173–4182, (2021).
Google Scholar
Yuan, R. et al. Chk1 and 14-3-3 proteins inhibit atypical E2Fs to prevent a permanent cell cycle arrest. EMBO J. 37, e97877 (2018).
Zhou, Y. et al. 1,3-Dicaffeoylquinic acid targeting 14-3-3 tau suppresses human breast cancer cell proliferation and metastasis through IL6/JAK2/PI3K pathway. Biochem. Pharm. 172, 113752 (2020).
Google Scholar
Ye, D. Z., Jin, S., Zhuo, Y. & Field, J. p21-Activated kinase 1 (Pak1) phosphorylates BAD directly at serine 111 in vitro and indirectly through Raf-1 at serine 112. PLoS One 6, e27637 (2011).
Google Scholar
Yan, Y. et al. Implication of 14-3-3epsilon and 14-3-3theta/tau in proteasome inhibition-induced apoptosis of glioma cells. Cancer Sci. 104, 55–61 (2013).
Google Scholar
Sun, Z. et al. 14-3-3zeta targets beta-catenin nuclear translocation to maintain mitochondrial homeostasis and promote the balance between proliferation and apoptosis in cisplatin-induced acute kidney injury. Cell Signal. 111, 110878 (2023).
Google Scholar
Shen, Q. et al. Overexpression of the 14-3-3gamma protein in uterine leiomyoma cells results in growth retardation and increased apoptosis. Cell Signal. 45, 43–53 (2018).
Google Scholar
Levine, B. & Kroemer, G. Biological functions of autophagy genes: a disease perspective. Cell 176, 11–42 (2019).
Google Scholar
Tang, Y. et al. 14-3-3zeta binds to and stabilizes phospho-beclin 1(S295) and induces autophagy in hepatocellular carcinoma cells. J. Cell Mol. Med. 24, 954–964 (2020).
Google Scholar
Zheng, Z., Zhong, Q. & Yan, X. YWHAE/14-3-3epsilon crotonylation regulates leucine deprivation-induced autophagy. Autophagy 19, 2401–2402 (2023).
Google Scholar
Robichaud, S. et al. Identification of novel lipid droplet factors that regulate lipophagy and cholesterol efflux in macrophage foam cells. Autophagy 17, 3671–3689 (2021).
Google Scholar
Kleppe, R., Martinez, A., Doskeland, S. O. & Haavik, J. The 14-3-3 proteins in regulation of cellular metabolism. Semin. Cell Dev. Biol. 22, 713–719 (2011).
Google Scholar
Meek, S. E., Lane, W. S. & Piwnica-Worms, H. Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins. J. Biol. Chem. 279, 32046–32054 (2004).
Google Scholar
Benton, R., Palacios, I. M. & St Johnston, D. Drosophila 14-3-3/PAR-5 is an essential mediator of PAR-1 function in axis formation. Dev. Cell 3, 659–671 (2002).
Google Scholar
Ding, J. et al. 14-3-3zeta is involved in the anticancer effect of metformin in colorectal carcinoma. Carcinogenesis 39, 493–502 (2018).
Google Scholar
Tong, Y. et al. KAT2A succinyltransferase activity-mediated 14-3-3zeta upregulation promotes beta-catenin stabilization-dependent glycolysis and proliferation of pancreatic carcinoma cells. Cancer Lett. 469, 1–10 (2020).
Google Scholar
Phan, L. et al. The cell cycle regulator 14-3-3sigma opposes and reverses cancer metabolic reprogramming. Nat. Commun. 6, 7530 (2015).
Google Scholar
Thorson, J. A. et al. 14-3-3 proteins are required for maintenance of Raf-1 phosphorylation and kinase activity. Mol. Cell. Biol. 18, 5229–5238 (1998).
Google Scholar
Fischer, A. et al. Regulation of RAF activity by 14-3-3 proteins: RAF kinases associate functionally with both homo- and heterodimeric forms of 14-3-3 proteins. J. Biol. Chem. 284, 3183–3194 (2009).
Google Scholar
Shaul, Y. D. & Seger, R. The MEK/ERK cascade: from signaling specificity to diverse functions. Biochim. Biophys. Acta 1773, 1213–1226 (2007).
Google Scholar
Xing, H., Zhang, S., Weinheimer, C., Kovacs, A. & Muslin, A. J. 14-3-3 proteins block apoptosis and differentially regulate MAPK cascades. EMBO J. 19, 349–358 (2000).
Google Scholar
Nordgaard, C. et al. Regulation of the Golgi apparatus by p38 and jnk kinases during cellular stress responses. Int. J. Mol. Sci. 22, 9595 (2021).
Gomez-Suarez, M. et al. 14-3-3 Proteins regulate Akt Thr308 phosphorylation in intestinal epithelial cells. Cell Death Differ. 23, 1060–1072 (2016).
Google Scholar
Muslin, A. J. & Xing, H. 14-3-3 proteins: regulation of subcellular localization by molecular interference. Cell Signal. 12, 703–709 (2000).
Google Scholar
Tzivion, G., Dobson, M. & Ramakrishnan, G. FoxO transcription factors; Regulation by AKT and 14-3-3 proteins. Biochim. Biophys. Acta 1813, 1938–1945 (2011).
Google Scholar
Neal, C. L. et al. Overexpression of 14-3-3zeta in cancer cells activates PI3K via binding the p85 regulatory subunit. Oncogene 31, 897–906 (2012).
Google Scholar
Ursini-Siegel, J. et al. The ShcA SH2 domain engages a 14-3-3/PI3’K signaling complex and promotes breast cancer cell survival. Oncogene 31, 5038–5044 (2012).
Google Scholar
Su, Y. W. et al. 14-3-3sigma regulates B-cell homeostasis through stabilization of FOXO1. Proc. Natl. Acad. Sci. USA 108, 1555–1560 (2011).
Google Scholar
Hata, A. & Chen, Y. G. TGF-beta signaling from receptors to Smads. Cold Spring Harb. Perspect. Biol. 8, a022061 (2016).
Zakharchenko, O., Cojoc, M., Dubrovska, A. & Souchelnytskyi, S. A role of TGFss1 dependent 14-3-3sigma phosphorylation at Ser69 and Ser74 in the regulation of gene transcription, stemness, and radioresistance. PloS One 8, e65163 (2013).
Google Scholar
Peng, D., Fu, M., Wang, M., Wei, Y. & Wei, X. Targeting TGF-beta signal transduction for fibrosis and cancer therapy. Mol. Cancer 21, 104 (2022).
Google Scholar
Dovrat, S. et al. 14-3-3 and beta-catenin are secreted on extracellular vesicles to activate the oncogenic Wnt pathway. Mol. Oncol. 8, 894–911 (2014).
Google Scholar
Lai, X. J. et al. Selective 14-3-3gamma induction quenches p-beta-catenin Ser37/Bax-enhanced cell death in cerebral cortical neurons during ischemia. Cell Death Dis. 5, e1184 (2014).
Google Scholar
Chang, T. C. et al. 14-3-3sigma regulates beta-catenin-mediated mouse embryonic stem cell proliferation by sequestering GSK-3beta. PloS One 7, e40193 (2012).
Google Scholar
Valenta, T., Hausmann, G. & Basler, K. The many faces and functions of beta-catenin. EMBO J. 31, 2714–2736 (2012).
Google Scholar
Koelman, E. M. R., Yeste-Vazquez, A. & Grossmann, T. N. Targeting the interaction of beta-catenin and TCF/LEF transcription factors to inhibit oncogenic Wnt signaling. Bioorg. Med. Chem. 70, 116920 (2022).
Google Scholar
Freeman, A. K. & Morrison, D. K. 14-3-3 Proteins: diverse functions in cell proliferation and cancer progression. Semin. Cell Dev. Biol. 22, 681–687 (2011).
Google Scholar
Schlegelmilch, K. et al. Yap1 acts downstream of alpha-catenin to control epidermal proliferation. Cell 144, 782–795 (2011).
Google Scholar
Habbig, S. et al. NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway. J. Cell Biol. 193, 633–642 (2011).
Google Scholar
Zuo, S. et al. 14-3-3 epsilon dynamically interacts with key components of mitogen-activated protein kinase signal module for selective modulation of the TNF-alpha-induced time course-dependent NF-kappaB activity. J. Proteome Res. 9, 3465–3478 (2010).
Google Scholar
Matitau, A. E. & Scheid, M. P. Phosphorylation of MEKK3 at threonine 294 promotes 14-3-3 association to inhibit nuclear factor kappa B activation. J. Biol. Chem. 283, 13261–13268 (2008).
Google Scholar
Liu, C. J. Progranulin: a promising therapeutic target for rheumatoid arthritis. FEBS Lett. 585, 3675–3680 (2011).
Google Scholar
Liu, C. J. & Bosch, X. Progranulin: a growth factor, a novel TNFR ligand, and a drug target. Pharmacol. Ther. 133, 124–132 (2012).
Google Scholar
Cui, Y., Hettinghouse, A. & Liu, C. J. Progranulin: a conductor of receptors orchestra, a chaperone of lysosomal enzymes and a therapeutic target for multiple diseases. Cytokine Growth Factor Rev. 45, 53–64 (2019).
Google Scholar
Jian, J., Konopka, J. & Liu, C. Insights into the role of progranulin in immunity, infection, and inflammation. J. Leukoc. Biol. 93, 199–208 (2012).
Jian, J., Li, G., Hettinghouse, A. & Liu, C. Progranulin: a key player in autoimmune diseases. Cytokine 101, 48–55 (2016).
Huang, G., Jian, J. & Liu, C. J. Progranulinopathy: a diverse realm of disorders linked to progranulin imbalances. Cytokine Growth Factor Rev. 76, 142–159 (2024).
Google Scholar
Fu, W., Hettinghouse, A. & Liu, C. J. In vitro, physical and functional interaction assays to examine the binding of progranulin derivative atsttrin to TNFR2 and its anti-TNFalpha activity. Methods Mol. Biol. 2248, 109–119 (2021).
Google Scholar
Moradi, L. et al. Injectable hydrogel for sustained delivery of progranulin derivative Atsttrin in treating diabetic fracture healing. Biomaterials 301, 122289 (2023).
Google Scholar
Wei, J. L. et al. Progranulin derivative Atsttrin protects against early osteoarthritis in mouse and rat models. Arthritis Res. Ther. 19, 280 (2017).
Google Scholar
Zhao, Y. P., Tian, Q. Y. & Liu, C. J. Progranulin deficiency exaggerates, whereas progranulin-derived Atsttrin attenuates, severity of dermatitis in mice. FEBS Lett. 587, 1805–1810 (2013).
Google Scholar
Hettinghouse, A., Fu, W. & Liu, C. J. Monitoring atsttrin-mediated inhibition of TNFalpha/NF-kappabeta activation through in vivo bioluminescence imaging. Methods Mol. Biol. 2248, 201–210 (2021).
Google Scholar
Katyal, P. et al. Injectable recombinant block polymer gel for sustained delivery of therapeutic protein in post traumatic osteoarthritis. Biomaterials 281, 121370 (2022).
Google Scholar
Zhao, Y. P. et al. Progranulin protects against osteoarthritis through interacting with TNF-alpha and beta-Catenin signalling. Ann. Rheum. Dis. 74, 2244–2253 (2015).
Google Scholar
Aguilera, C. et al. Efficient nuclear export of p65-IkappaBalpha complexes requires 14-3-3 proteins. J. Cell Sci. 119, 3695–3704 (2006).
Google Scholar
Ingles-Esteve, J. et al. Inhibition of specific NF-kappaB activity contributes to the tumor suppressor function of 14-3-3sigma in breast cancer. PloS One 7, e38347 (2012).
Google Scholar
Hartman, A. M. & Hirsch, A. K. H. Molecular insight into specific 14-3-3 modulators: Inhibitors and stabilisers of protein-protein interactions of 14-3-3. Eur. J. Med. Chem. 136, 573–584 (2017).
Google Scholar
Mori, M., Vignaroli, G. & Botta, M. Small molecules modulation of 14-3-3 protein-protein interactions. Drug Discov. Today Technol. 10, e541–547 (2013).
Google Scholar
Zhao, J., Meyerkord, C. L., Du, Y., Khuri, F. R. & Fu, H. 14-3-3 proteins as potential therapeutic targets. Semin. Cell Dev. Biol. 22, 705–712 (2011).
Google Scholar
Milroy, L. G., Brunsveld, L. & Ottmann, C. Stabilization and inhibition of protein-protein interactions: the 14-3-3 case study. ACS Chem. Biol. 8, 27–35 (2013).
Google Scholar
Tian, Q., He, X. C., Hood, L. & Li, L. Bridging the BMP and Wnt pathways by PI3 kinase/Akt and 14-3-3zeta. Cell Cycle 4, 215–216 (2005).
Google Scholar
Batra, N., Riquelme, M. A., Burra, S. & Jiang, J. X. 14-3-3theta facilitates plasma membrane delivery and function of mechanosensitive connexin 43 hemichannels. J. Cell Sci. 127, 137–146 (2014).
Google Scholar
Bronisz, A. et al. Microphthalmia-associated transcription factor interactions with 14-3-3 modulate differentiation of committed myeloid precursors. Mol. Biol. Cell 17, 3897–3906 (2006).
Google Scholar
Aldana, A. A., Uhart, M., Abraham, G. A., Bustos, D. M. & Boccaccini, A. R. 14-3-3epsilon protein-loaded 3D hydrogels favor osteogenesis. J. Mater. Sci. Mater. Med. 31, 105 (2020).
Google Scholar
Liu, Y., Ross, J. F., Bodine, P. V. & Billiard, J. Homodimerization of Ror2 tyrosine kinase receptor induces 14-3-3(beta) phosphorylation and promotes osteoblast differentiation and bone formation. Mol. Endocrinol. 21, 3050–3061 (2007).
Google Scholar
Kong, D. et al. Procoxacin bidirectionally inhibits osteoblastic and osteoclastic activity in bone and suppresses bone metastasis of prostate cancer. J. Exp. Clin. Cancer Res. 42, 45 (2023).
Google Scholar
Schwarz, T., Murphy, S., Sohn, C. & Mansky, K. C. C-TAK1 interacts with microphthalmia-associated transcription factor, MITF, but not the related family member Tfe3. Biochem. Biophys. Res. Commun. 394, 890–895 (2010).
Google Scholar
van Beers-Tas, M. H., Marotta, A., Boers, M., Maksymowych, W. P. & van Schaardenburg, D. A prospective cohort study of 14-3-3eta in ACPA and/or RF-positive patients with arthralgia. Arthritis Res. Ther. 18, 76 (2016).
Google Scholar
Grozinger, C. M. & Schreiber, S. L. Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization. Proc. Natl. Acad. Sci. 97, 7835–7840 (2000).
Google Scholar
Miska, E. A. et al. Differential localization of HDAC4 orchestrates muscle differentiation. Nucleic Acids Res. 29, 3439–3447 (2001).
Google Scholar
Guan, Y. et al. Subcellular relocation of histone deacetylase 4 regulates growth plate chondrocyte differentiation through Ca2+/calmodulin-dependent kinase IV. Am. J. Physiol. Cell Physiol. 303, C33–40 (2012).
Google Scholar
Frontini-Lopez, Y. R., Gojanovich, A. D., Del Veliz, S., Uhart, M. & Bustos, D. M. 14-3-3beta isoform is specifically acetylated at Lys51 during differentiation to the osteogenic lineage. J. Cell. Biochem. 122, 1767–1780 (2021).
Google Scholar
Nishimori, S., Wein, M. N. & Kronenberg, H. M. PTHrP targets salt-inducible kinases, HDAC4 and HDAC5, to repress chondrocyte hypertrophy in the growth plate. Bone 142, 115709 (2021).
Google Scholar
Pandey, A. & Bhutani, N. Profiling joint tissues at single-cell resolution: advances and insights. Nat. Rev. Rheumatol. 20, 7–20 (2024).
Google Scholar
Kadiri, M. et al. 14-3-3eta Promotes invadosome formation via the FOXO3-snail axis in rheumatoid arthritis fibroblast-like synoviocytes. Int. J. Mol. Sci. 23, 123 (2021).
Barry, E. F. et al. 14-3-3:Shc scaffolds integrate phosphoserine and phosphotyrosine signaling to regulate phosphatidylinositol 3-kinase activation and cell survival. J. Biol. Chem. 284, 12080–12090 (2009).
Google Scholar
Jiang, J. et al. 14-3-3 regulates the LNK/JAK2 pathway in mouse hematopoietic stem and progenitor cells. J. Clin. Investig. 122, 2079–2091 (2012).
Google Scholar
Zhao, R. et al. MiR-204/14-3-3zeta axis regulates osteosarcoma cell proliferation through SATA3 pathway. Die Pharm. 72, 593–598 (2017).
Google Scholar
Choi, E. Y. et al. Regulation of LFA-1-dependent inflammatory cell recruitment by Cbl-b and 14-3-3 proteins. Blood 111, 3607–3614 (2008).
Google Scholar
Zhou, R. P. et al. Modulators of ASIC1a and its potential as a therapeutic target for age-related diseases. Ageing Res. Rev. 83, 101785 (2023).
Google Scholar
Lai, Y. et al. ADAMTS-7 forms a positive feedback loop with TNF-alpha in the pathogenesis of osteoarthritis. Ann. Rheum. Dis. 73, 1575–1584 (2014).
Google Scholar
Lin, E. A. & Liu, C. J. The emerging roles of ADAMTS-7 and ADAMTS-12 matrix metalloproteinases. Open Acess Rheumatol. 1,121–131 (2009).
Lin, E. A. & Liu, C. J. The role of ADAMTSs in arthritis. Protein Cell 1, 33–47 (2010).
Google Scholar
Lee, S. W. et al. A purified extract from clematis mandshurica prevents staurosporin-induced downregulation of 14-3-3 and subsequent apoptosis on rat chondrocytes. J. Ethnopharmacol. 111, 213–218 (2007).
Google Scholar
Yao, Q. et al. Osteoarthritis: pathogenic signaling pathways and therapeutic targets. Signal Transduct. Target Ther. 8, 56 (2023).
Google Scholar
Chijimatsu, R. & Saito, T. Mechanisms of synovial joint and articular cartilage development. Cell Mol. Life Sci. 76, 3939–3952 (2019).
Google Scholar
Deng, Z. H., Li, Y. S., Gao, X., Lei, G. H. & Huard, J. Bone morphogenetic proteins for articular cartilage regeneration. Osteoarthr. Cartil. 26, 1153–1161 (2018).
Google Scholar
Yin, B. et al. Harnessing tissue-derived extracellular vesicles for osteoarthritis theranostics. Theranostics 12, 207–231 (2022).
Google Scholar
Gardino, A. K. & Yaffe, M. B. 14-3-3 proteins as signaling integration points for cell cycle control and apoptosis. Semin Cell Dev. Biol. 22, 688–695 (2011).
Google Scholar
Tan, Y., Ruan, H., Demeter, M. R. & Comb, M. J. p90(RSK) blocks bad-mediated cell death via a protein kinase C-dependent pathway. J. Biol. Chem. 274, 34859–34867 (1999).
Google Scholar
Priam, S. et al. Identification of soluble 14-3-3∊ as a novel subchondral bone mediator involved in cartilage degradation in osteoarthritis. Arthritis Rheum. 65, 1831–1842 (2013).
Google Scholar
Nefla, M. et al. The pro-inflammatory cytokine 14-3-3epsilon is a ligand of CD13 in cartilage. J. Cell Sci. 128, 3250–3262 (2015).
Google Scholar
Ghaffari, A., Li, Y., Kilani, R. T. & Ghahary, A. 14-3-3 sigma associates with cell surface aminopeptidase N in the regulation of matrix metalloproteinase-1. J. Cell Sci. 123, 2996–3005 (2010).
Google Scholar
Ali, S. A. et al. Circulating microRNAs differentiate fast-progressing from slow-progressing and non-progressing knee osteoarthritis in the osteoarthritis initiative cohort. Ther. Adv. Musculoskelet. Dis. 14, 1759720X221082917 (2022).
Google Scholar
Hulme, C. H. et al. Identification of candidate synovial fluid biomarkers for the prediction of patient outcome after microfracture or osteotomy. Am. J. Sports Med. 49, 1512–1523 (2021).
Google Scholar
Rockel, J. S. & Kapoor, M. The metabolome and osteoarthritis: possible contributions to symptoms and pathology. Metabolites 8, 92 (2018).
Huang, J. et al. Association between higher triglyceride glucose index and increased risk of osteoarthritis: data from NHANES 2015-2020. BMC Public Health 24, 758 (2024).
Google Scholar
Chiba, D. et al. Higher fasting blood glucose worsens knee symptoms in patients with radiographic knee osteoarthritis and comorbid central sensitization: an Iwaki cohort study. Arthritis Res. Ther. 24, 269 (2022).
Google Scholar
Ji, L. et al. The 14-3-3 protein YWHAB inhibits glucagon-induced hepatic gluconeogenesis through interacting with the glucagon receptor and FOXO1. FEBS Lett. 595, 1275–1288 (2021).
Google Scholar
Neumann, J. et al. Type 2 diabetes patients have accelerated cartilage matrix degeneration compared to diabetes free controls: data from the Osteoarthritis Initiative. Osteoarthr. Cartil. 26, 751–761 (2018).
Google Scholar
Thandavarayan, R. A. et al. 14-3-3 protein regulates Ask1 signaling and protects against diabetic cardiomyopathy. Biochem. Pharmacol. 75, 1797–1806 (2008).
Google Scholar
Lim, G. E. et al. 14-3-3zeta coordinates adipogenesis of visceral fat. Nat. Commun. 6, 7671 (2015).
Google Scholar
Williams, A., Wang, E. C., Thurner, L. & Liu, C. J. Review: novel insights into tumor necrosis factor receptor, death receptor 3, and progranulin pathways in arthritis and bone remodeling. Arthritis Rheumatol. 68, 2845–2856 (2016).
Google Scholar
Xu, Y. & Chen, F. Acid-sensing ion channel-1a in articular chondrocytes and synovial fibroblasts: a novel therapeutic target for rheumatoid arthritis. Front. Immunol. 11, 580936 (2020).
Google Scholar
Gravallese, E. M. & Firestein, G. S. Rheumatoid arthritis – common origins, divergent mechanisms. N. Engl. J. Med. 388, 529–542 (2023).
Google Scholar
Zeng, T., Tan, L., Wu, Y. & Yu, J. 14-3-3eta protein in rheumatoid arthritis: promising diagnostic marker and independent risk factor for osteoporosis. Lab. Med. 51, 529–539 (2020).
Google Scholar
Hammam, N., Salah, S., Kholef, E. F., Moussa, E. M. & Marotta, A. 14-3-3eta protein in serum and synovial fluid correlates with radiographic damage and progression in a longitudinal evaluation of patients with established rheumatoid arthritis. Mod. Rheumatol. 30, 664–670 (2020).
Google Scholar
Hirata, S., Marotta, A., Gui, Y., Hanami, K. & Tanaka, Y. Serum 14-3-3eta level is associated with severity and clinical outcomes of rheumatoid arthritis, and its pretreatment level is predictive of DAS28 remission with tocilizumab. Arthritis Res. Ther. 17, 280 (2015).
Google Scholar
Maksymowych, W. P. et al. Serum 14-3-3eta is a novel marker that complements current serological measurements to enhance detection of patients with rheumatoid arthritis. J. Rheumatol. 41, 2104–2113 (2014).
Google Scholar
Zhang, Y. et al. ASIC1a induces synovial inflammation via the Ca2+/NFATc3/ RANTES pathway. Theranostics 10, 247–264 (2020).
Google Scholar
Xu, Y. et al. Acid sensor ASIC1a induces synovial fibroblast proliferation via Wnt/beta-catenin/c-Myc pathway in rheumatoid arthritis. Int. Immunopharmacol. 113, 109328 (2022).
Google Scholar
Niu, R. et al. ASIC1a promotes synovial invasion of rheumatoid arthritis via Ca2+/Rac1 pathway. Int. Immunopharmacol. 79, 106089 (2020).
Google Scholar
Wei, F. et al. PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner. Sci. Rep. 4, 7023 (2014).
Google Scholar
Wei, J. L., Buza, J. 3rd & Liu, C. J. Does progranulin account for the opposite effects of etanercept and infliximab/adalimumab in osteoarthritis? Comment on Olson et al.: “Therapeutic opportunities to prevent post-traumatic arthritis: lessons from the natural history of arthritis after articular fracture”. J. Orthop. Res. 34, 12–14 (2016).
Google Scholar
Kilani, R. T. et al. Detection of high levels of 2 specific isoforms of 14-3-3 proteins in synovial fluid from patients with joint inflammation. J. Rheumatol. 34, 1650–1657 (2007).
Google Scholar
Huang, Y., Yang, M. & Huang, W. 14-3-3 sigma: a potential biomolecule for cancer therapy. Clin. Chim. Acta. Int. J. Clin. Chem. 511, 50–58 (2020).
Google Scholar
Meltzer, P. S. & Helman, L. J. New horizons in the treatment of osteosarcoma. N. Engl. J. Med. 385, 2066–2076 (2021).
Google Scholar
Gorlick, R. et al. Children’s Oncology group’s 2013 blueprint for research: bone tumors. Pediatr. Blood Cancer 60, 1009–1015 (2013).
Google Scholar
Kager, L. et al. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J. Clin. Oncol. 21, 2011–2018 (2003).
Google Scholar
Yang, Z. et al. 14-3-3sigma downregulation suppresses ICC metastasis via impairing migration, invasion, and anoikis resistance of ICC cells. Cancer Biomark. 19, 313–325 (2017).
Google Scholar
Xiao, Y. et al. 14-3-3tau promotes breast cancer invasion and metastasis by inhibiting RhoGDIalpha. Mol. Cell Biol. 34, 2635–2649 (2014).
Google Scholar
Hao, X. et al. CircPAK1 promotes the progression of hepatocellular carcinoma via modulation of YAP nucleus localization by interacting with 14-3-3zeta. J. Exp. Clin. Cancer Res. 41, 281 (2022).
Google Scholar
Chu, Y. W., Wang, C. R., Weng, F. B., Yan, Z. J. & Wang, C. MicroRNA-222 contributed to cell proliferation, invasion and migration via regulating YWHAG in osteosarcoma. Eur. Rev. Med. Pharm. Sci. 22, 2588–2597 (2018).
Kim, K. O. et al. Proteomic identification of 14-3-3ϵ as a linker protein between pERK1/2 inhibition and BIM upregulation in human osteosarcoma cells. J. Orthop. Res. 32, 848–854 (2014).
Google Scholar
Ahrens, W. A., Ridenour, R. V. 3rd, Caron, B. L., Miller, D. V. & Folpe, A. L. GLUT-1 expression in mesenchymal tumors: an immunohistochemical study of 247 soft tissue and bone neoplasms. Hum. Pathol. 39, 1519–1526 (2008).
Google Scholar
Ngo, S., Barry, J. B., Nisbet, J. C., Prins, J. B. & Whitehead, J. P. Reduced phosphorylation of AS160 contributes to glucocorticoid-mediated inhibition of glucose uptake in human and murine adipocytes. Mol. Cell. Endocrinol. 302, 33–40 (2009).
Google Scholar
Shan, H. J., Gu, W. X., Duan, G. & Chen, H. L. Fat mass and obesity-associated (FTO)-mediated N6-methyladenosine modification of Kruppel-like factor 3 (KLF3) promotes osteosarcoma progression. Bioengineered 13, 8038–8050 (2022).
Google Scholar
Bereza, M. et al. Epigenetic abnormalities in chondrosarcoma. Int. J. Mol. Sci. 24, 4539 (2023).
Rock, A., Ali, S. & Chow, W. A. Systemic therapy for chondrosarcoma. Curr. Treat. Options Oncol. 23, 199–209 (2022).
Google Scholar
Giuffrida, A. Y. et al. Chondrosarcoma in the United States (1973 to 2003): an analysis of 2890 cases from the SEER database. J. Bone Jt. Surg. Am. 91, 1063–1072 (2009).
Google Scholar
Evans, H. L., Ayala, A. G. & Romsdahl, M. M. Prognostic factors in chondrosarcoma of bone: a clinicopathologic analysis with emphasis on histologic grading. Cancer 40, 818–831 (1977).
Gelderblom, H. et al. The clinical approach towards chondrosarcoma. Oncologist 13, 320–329 (2008).
Google Scholar
Whelan, J. S. & Davis, L. E. Osteosarcoma, chondrosarcoma, and chordoma. J. Clin. Oncol. 36, 188–193 (2018).
Google Scholar
Yang, W. H. et al. Epigallocatechin-3-gallate induces cell apoptosis of human chondrosarcoma cells through apoptosis signal-regulating kinase 1 pathway. J. Cell Biochem. 112, 1601–1611 (2011).
Google Scholar
Kidd, M. E., Shumaker, D. K. & Ridge, K. M. The role of vimentin intermediate filaments in the progression of lung cancer. Am. J. Respir. Cell Mol. Biol. 50, 1–6 (2014).
Google Scholar
Wu, Y. J., Jan, Y. J., Ko, B. S., Liang, S. M. & Liou, J. Y. Involvement of 14-3-3 proteins in regulating tumor progression of hepatocellular carcinoma. Cancers 7, 1022–1036 (2015).
Google Scholar
Lee, J. X. T. et al. YWHAG deficiency disrupts the EMT-associated network to induce oxidative cell death and prevent metastasis. Adv. Sci. 10, e2301714 (2023).
Google Scholar
Shinohara, N. et al. TGF-beta signalling and PEG10 are mutually exclusive and inhibitory in chondrosarcoma cells. Sci. Rep. 7, 13494 (2017).
Google Scholar
Hong, H. Y., Jeon, W. K., Kim, S. J. & Kim, B. C. 14-3-3 sigma is a new target up-regulated by transforming growth factor-beta1 through a Smad3-dependent mechanism. Biochem. Biophys. Res. Commun. 432, 193–197 (2013).
Google Scholar
Xu, J. et al. 14-3-3zeta turns TGF-beta’s function from tumor suppressor to metastasis promoter in breast cancer by contextual changes of Smad partners from p53 to Gli2. Cancer Cell 27, 177–192 (2015).
Google Scholar
Li, G. et al. Slug signaling is up-regulated by CCL21/CCR7 [corrected] to induce EMT in human chondrosarcoma. Med. Oncol. 32, 478 (2015).
Google Scholar
Huang, X. Y. et al. alphaB-crystallin complexes with 14-3-3zeta to induce epithelial-mesenchymal transition and resistance to sorafenib in hepatocellular carcinoma. Hepatology 57, 2235–2247 (2013).
Google Scholar
Raychaudhuri, K. et al. 14-3-3sigma gene loss leads to activation of the epithelial to mesenchymal transition due to the stabilization of c-jun protein. J. Biol. Chem. 291, 16068–16081 (2016).
Google Scholar
Cowan, A. J. et al. Diagnosis and management of multiple myeloma: a review. JAMA 327, 464–477 (2022).
Google Scholar
Cowan, A. J. et al. Global burden of multiple myeloma: a systematic analysis for the global burden of disease study 2016. JAMA Oncol. 4, 1221–1227 (2018).
Google Scholar
Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin. 70, 7–30 (2020).
Google Scholar
Minnie, S. A. & Hill, G. R. Immunotherapy of multiple myeloma. J. Clin. Investig. 130, 1565–1575 (2020).
Google Scholar
Diaz de la Guardia, R. et al. Expression profile of telomere-associated genes in multiple myeloma. J. Cell Mol. Med. 16, 3009–3021 (2012).
Google Scholar
Obeng, E. A. et al. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood 107, 4907–4916 (2006).
Google Scholar
Bianchi, G. et al. The proteasome load versus capacity balance determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition. Blood 113, 3040–3049 (2009).
Google Scholar
Gu, Y. et al. 14-3-3zeta binds the proteasome, limits proteolytic function, and enhances sensitivity to proteasome inhibitors. Leukemia 32, 744–751 (2018).
Google Scholar
Takahashi, T. et al. Synergistic combination therapy with cotylenin A and vincristine in multiple myeloma models. Int. J. Oncol. 46, 1801–1809 (2015).
Google Scholar
Dehlin, M., Jacobsson, L. & Roddy, E. Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors. Nat. Rev. Rheumatol. 16, 380–390 (2020).
Google Scholar
Wijnands, J. M. et al. Determinants of the prevalence of gout in the general population: a systematic review and meta-regression. Eur. J. Epidemiol. 30, 19–33 (2015).
Google Scholar
Dogan, I. et al. 14-3-3 eta ETA protein as a potential marker of joint damage in gout. Clin. Biochem. 118, 110611 (2023).
Google Scholar
Phipps-Green, A. J. et al. Twenty-eight loci that influence serum urate levels: analysis of association with gout. Ann. Rheum. Dis. 75, 124–130 (2016).
Google Scholar
Martinon, F. & Glimcher, L. H. Gout: new insights into an old disease. J. Clin. Investig. 116, 2073–2075 (2006).
Google Scholar
van de Veerdonk, F. L., Netea, M. G., Dinarello, C. A. & Joosten, L. A. Inflammasome activation and IL-1beta and IL-18 processing during infection. Trends Immunol. 32, 110–116 (2011).
Google Scholar
Tran, T. H., Pham, J. T., Shafeeq, H., Manigault, K. R. & Arya, V. Role of interleukin-1 inhibitors in the management of gout. Pharmacotherapy 33, 744–753 (2013).
Google Scholar
Liu, Y. R., Wang, J. Q. & Li, J. Role of NLRP3 in the pathogenesis and treatment of gout arthritis. Front. Immunol. 14, 1137822 (2023).
Google Scholar
Reid, I. R. & Billington, E. O. Drug therapy for osteoporosis in older adults. Lancet 399, 1080–1092 (2022).
Google Scholar
Johnston, C. B. & Dagar, M. Osteoporosis in older adults. Med. Clin. North Am. 104, 873–884 (2020).
Google Scholar
Johnell, O. & Kanis, J. A. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos. Int. 17, 1726–1733 (2006).
Google Scholar
Kanis, J. A. et al. Long-term risk of osteoporotic fracture in Malmo. Osteoporos. Int. 11, 669–674 (2000).
Google Scholar
Jiang, H. X. et al. Development and initial validation of a risk score for predicting in-hospital and 1-year mortality in patients with hip fractures. J. Bone Min. Res. 20, 494–500 (2005).
Google Scholar
Vilaca, T., Eastell, R. & Schini, M. Osteoporosis in men. Lancet Diabetes Endocrinol. 10, 273–283 (2022).
Google Scholar
Anish, R. J. & Nair, A. Osteoporosis management-current and future perspectives—a systemic review. J. Orthop. 53, 101–113 (2024).
Google Scholar
Huang, J., Huang, J., Hu, W. & Zhang, Z. Heat shock protein 90 alpha and 14-3-3eta in postmenopausal osteoporotic rats with varying levels of serum FSH. Climacteric 23, 581–590 (2020).
Google Scholar
Abdelhafiz, D., Baker, T., Glascow, D. A. & Abdelhafiz, A. Biomarkers for the diagnosis and treatment of rheumatoid arthritis—a systematic review. Postgrad. Med. 135, 214–223 (2023).
Google Scholar
Tao, H. et al. Urolithin A suppresses RANKL-induced osteoclastogenesis and postmenopausal osteoporosis by, suppresses inflammation and downstream NF-kappaB-activated pyroptosis pathways. Pharm. Res. 174, 105967 (2021).
Google Scholar
An, Y. et al. Activation of ROS/MAPKs/NF-kappaB/NLRP3 and inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis. FASEB J. 33, 12515–12527 (2019).
Google Scholar
Li, Y. et al. Urolithin B suppressed osteoclast activation and reduced bone loss of osteoporosis via inhibiting ERK/NF-kappaB pathway. Cell Prolif. 55, e13291 (2022).
Google Scholar
Li, S. et al. 14-3-3 protein of neospora caninum modulates host cell innate immunity through the activation of MAPK and NF-kappaB pathways. Front. Microbiol. 10, 37 (2019).
Google Scholar
Yang, T. et al. RDIVpSGP motif of ASPP2 binds to 14-3-3 and enhances ASPP2/k18/14-3-3 ternary complex formulation to promote BRAF/MEK/ERK signal-inhibited cell proliferation in hepatocellular carcinoma. Cancer Gene Ther. 29, 1616–1627 (2022).
Google Scholar
Ottmann, C. et al. A structural rationale for selective stabilization of anti-tumor interactions of 14-3-3 proteins by cotylenin A. J. Mol. Biol. 386, 913–919 (2009).
Google Scholar
Anders, C. et al. A semisynthetic fusicoccane stabilizes a protein-protein interaction and enhances the expression of K+ channels at the cell surface. Chem. Biol. 20, 583–593 (2013).
Google Scholar
Bier, D. et al. Small-molecule stabilization of the 14-3-3/Gab2 protein-protein interaction (PPI) interface. Chem. Med. Chem. 11, 911–918 (2016).
Google Scholar
Rose, R. et al. Identification and structure of small-molecule stabilizers of 14-3-3 protein-protein interactions. Angew. Chem. Int. Ed. Engl. 49, 4129–4132 (2010).
Google Scholar
Richter, A., Rose, R., Hedberg, C., Waldmann, H. & Ottmann, C. An optimised small-molecule stabiliser of the 14-3-3-PMA2 protein-protein interaction. Chemistry 18, 6520–6527 (2012).
Google Scholar
Sato, S. et al. Metabolite regulation of nuclear localization of carbohydrate-response element-binding protein (ChREBP): role of AMP as an allosteric inhibitor. J. Biol. Chem. 291, 10515–10527 (2016).
Google Scholar
Takahashi, S., Wakui, H., Gustafsson, J. A., Zilliacus, J. & Itoh, H. Functional interaction of the immunosuppressant mizoribine with the 14-3-3 protein. Biochem. Biophys. Res. Commun. 274, 87–92 (2000).
Google Scholar
Mancini, M. et al. A new nonpeptidic inhibitor of 14-3-3 induces apoptotic cell death in chronic myeloid leukemia sensitive or resistant to imatinib. J. Pharm. Exp. Ther. 336, 596–604 (2011).
Google Scholar
Zhao, J. et al. Discovery and structural characterization of a small molecule 14-3-3 protein-protein interaction inhibitor. Proc. Natl. Acad. Sci. USA 108, 16212–16216 (2011).
Google Scholar
Ottmann, C. et al. Structure of a 14-3-3 coordinated hexamer of the plant plasma membrane H+ -ATPase by combining X-ray crystallography and electron cryomicroscopy. Mol. Cell 25, 427–440 (2007).
Google Scholar
Wu, H., Ge, J. & Yao, S. Q. Microarray-assisted high-throughput identification of a cell-permeable small-molecule binder of 14-3-3 proteins. Angew. Chem. Int. Ed. Engl. 49, 6528–6532 (2010).
Google Scholar
Aghazadeh, Y. & Papadopoulos, V. The role of the 14-3-3 protein family in health, disease, and drug development. Drug Discov. Today 21, 278–287 (2016).
Google Scholar
Arrendale, A. et al. Synthesis of a phosphoserine mimetic prodrug with potent 14-3-3 protein inhibitory activity. Chem. Biol. 19, 764–771 (2012).
Google Scholar
Corradi, V. et al. Computational techniques are valuable tools for the discovery of protein-protein interaction inhibitors: the 14-3-3σ case. Bioorg. Med. Chem. Lett. 21, 6867–6871 (2011).
Google Scholar
Mori, M. et al. Discovery of 14-3-3 protein-protein interaction inhibitors that sensitize multidrug-resistant cancer cells to doxorubicin and the Akt inhibitor GSK690693. Chem. Med. Chem. 9, 973–983 (2014).
Google Scholar
Park, K. D. et al. Identification of a lacosamide binding protein using an affinity bait and chemical reporter strategy: 14-3-3 ζ. J. Am. Chem. Soc. 133, 11320–11330 (2011).
Google Scholar
Ottmann, C. Small-molecule modulators of 14-3-3 protein-protein interactions. Bioorg. Med. Chem. 21, 4058–4062 (2013).
Google Scholar
Sawada, M. et al. Synthesis and anti-migrative evaluation of moverastin derivatives. Bioorg. Med. Chem. Lett. 21, 1385–1389 (2011).
Google Scholar
Du, Y., Masters, S. C., Khuri, F. R. & Fu, H. Monitoring 14-3-3 protein interactions with a homogeneous fluorescence polarization assay. J. Biomol. Screen 11, 269–276 (2006).
Google Scholar
Bier, D. et al. Molecular tweezers modulate 14-3-3 protein-protein interactions. Nat. Chem. 5, 234–239 (2013).
Google Scholar
Masters, S. C. & Fu, H. 14-3-3 proteins mediate an essential anti-apoptotic signal. J. Biol. Chem. 276, 45193–45200 (2001).
Google Scholar
Aghazadeh, Y., Martinez-Arguelles, D. B., Fan, J., Culty, M. & Papadopoulos, V. Induction of androgen formation in the male by a TAT-VDAC1 fusion peptide blocking 14-3-3ɛ protein adaptor and mitochondrial VDAC1 interactions. Mol. Ther. 22, 1779–1791 (2014).
Google Scholar
Xu, Y. et al. YWHAE/14-3-3epsilon expression impacts the protein load, contributing to proteasome inhibitor sensitivity in multiple myeloma. Blood 136, 468–479 (2020).
Google Scholar
link
