Alternative titles; symbols
HGNC Approved Gene Symbol: YWHAB
Cytogenetic location: 20q13.12 Genomic coordinates (GRCh38): 20:44,885,705-44,908,532 (from NCBI)
The highly conserved 14-3-3 proteins are found in both plants and mammals; see YWHAH (113508) and YWHAZ (601288). Some have been shown to be involved in the activation of c-Raf (164760) by their participation in the protein kinase C signaling pathway (see 176960). Leffers et al. (1993) reported the cloning of 14-3-3 beta.
The 14-3-3 family of proteins mediates signal transduction by binding to phosphoserine-containing proteins. Using phosphoserine-oriented peptide libraries to probe all mammalian and yeast 14-3-3s, Yaffe et al. (1997) identified 2 different binding motifs, RSXpSXP and RXY/FXpSXP, present in nearly all known 14-3-3 binding proteins. The crystal structure of YWHAZ complexed with the phosphoserine motif in polyoma middle-T was determined to 2.6-angstrom resolution. The authors showed that the 14-3-3 dimer binds tightly to single molecules containing tandem repeats of phosphoserine motifs, implicating bidentate association as a signaling mechanism with molecules such as Raf, BAD (603167), and Cbl.
Using 2-hybrid experiments, Han et al. (1997) demonstrated interaction between murine Ywhab and the RAS-binding domain of RIN1 (605965).
Shumway et al. (2003) found that 14-3-3-beta interacts with the TSC1 (605284)-TSC2 (191092) dimer. The interaction required phosphorylation of TSC2 at ser1210. Binding of 14-3-3-beta to TSC2 did not alter the interaction between TSC1 and TSC2, but it reduced the ability of the complex to inhibit phosphorylation of ribosomal protein S6 kinase (608938), impairing the ability of the complex to inhibit cell growth.
Yang et al. (2014) had previously found that mouse seipin (BSCL2; 606158) promotes adipogenesis to accommodate storage of excess nutrients in the form of lipids, whereas it inhibits lipid droplet production and accumulation in preadipocytes and other nonadipocyte lineages. Using mass spectrometry to identify proteins that interacted with seipin in adipose tissue lysates, Yang et al. (2014) identified the scaffold protein 14-3-3-beta. Interaction of seipin with 14-3-3-beta did not depend on insulin stimulation. In insulin (INS; 176730)-stimulated 3T3-L1 mouse adipocytes, 14-3-3-beta interacted with the actin-severing protein cofilin-1 (CFL1; 601442), and this interaction required serine phosphorylation of cofilin-1. Adipogenesis in 3T3-L1 cells was accompanied by remodeling of the actin cytoskeleton from central stress fibers to the cell cortex, concomitant with lipid droplet accumulation. Knockdown of seipin, 14-3-3-beta, or cofilin-1 in 3T3-L1 cells impaired adipocyte development and inhibited lipid drop accumulation, but stress fibers remained intact. Impaired adipogenesis was also present in 3T3-L1 cells expressing a severing-resistant actin mutant. Yang et al. (2014) concluded that the interaction of seipin with 14-3-3-beta recruits cofilin-1 to remodel the actin cytoskeleton for adipocyte differentiation.
Tommerup and Leffers (1996) mapped the YWHAB gene to 20q13.1 by fluorescence in situ hybridization.
Han, L. Wong, D., Dhaka, A., Afar, D., White, M., Xie, W., Herschman, H., Witte, O. Colicelli, J.: Protein binding and signaling properties of RIN1 suggest a unique effector function. Proc. Nat. Acad. Sci. 94: 4954-4959, 1997. [PubMed: 9144171] [Full Text: https://doi.org/10.1073/pnas.94.10.4954]
Leffers, H., Madsen, P., Rasmussen, H. H., Honore, B., Andersen, A. H., Walbum, E., Vandekerckhove, J., Celis, J. E. Molecular cloning and expression of the transformation sensitive epithelial marker stratifin: a member of a protein family that has been involved in the protein kinase C signalling pathway. J. Molec. Biol. 231: 982-998, 1993. [PubMed: 8515476] [Full Text: https://doi.org/10.1006/jmbi.1993.1346]
Shumway, S. D., Li, Y., Xiong, Y. 14-3-3-beta binds to and negatively regulates the tuberous sclerosis complex 2 (TSC2) tumor suppressor gene product, tuberin. J. Biol. Chem. 278: 2089-2092, 2003. [PubMed: 12468542] [Full Text: https://doi.org/10.1074/jbc.C200499200]
Tommerup, N., Leffers, H. Assignment of the human genes encoding 14-3-3 eta (YWHAH) to 22q12, 14-3-3 zeta (YWHAZ) to 2p25.1-p25.2, and 14-3-3 beta (YWHAB) to 20q13.1 by in situ hybridization. Genomics 33: 149-150, 1996. [PubMed: 8617504] [Full Text: https://doi.org/10.1006/geno.1996.0176]
Yaffe, M. B., Rittinger, K., Volinia, S., Caron, P. R., Aitken, A., Leffers, H., Gamblin, S. J., Smerdon, S. J., Cantley, L. C. The structural basis for 14-3-3:phosphopeptide binding specificity. Cell 91: 961-971, 1997. [PubMed: 9428519] [Full Text: https://doi.org/10.1016/s0092-8674(00)80487-0]
Yang, W., Thein, S., Wang, X., Bi, X., Ericksen, R. E., Xu, F., Han, W. BSCL2/seipin regulates adipogenesis through actin cytoskeleton remodelling. Hum. Molec. Genet. 23: 502-513, 2014. [PubMed: 24026679] [Full Text: https://doi.org/10.1093/hmg/ddt444]