14-3-3 proteins regulate many cellular processes relevant to cancer biology, notably apoptosis, mitogenic signaling and cell-cycle checkpoints. Seven isoforms, denoted 14-3-3 b, g, e, z, h, q and s, comprise this family of signaling intermediates. 14-3-3 s, also known as SFN, stratifin, HME1 or YWHAS, is a secreted adaptor protein that is involved in regulating both general and specific signaling pathways. Expressed predominately in stratified squamous keratinising epithelium, 14-3-3 s is able to bind and modify the activity of a large number of proteins, such as KRT17 (Keratin 17), through recognition of a phosphothreonine or phosphoserine motif. When bound to Keratin 17, for example, 14-3-3 s acts to stimulate the Akt/mTOR signaling pathway by upregulating protein synthesis and cell growth. 14-3-3 s also functions to positively mediate IGF-I-induced cell cycle progression and can bind to a variety of translation initiation factors, thus controlling mitotic translation. In response to tumor growth, 14-3-3 s positively regulates the tumor suppressor p53 and increases the rate of p53-regulated inhibition of G2/M cell cycle progression. Multiple isoforms of 14-3-3 s exist due to alternative splicing events.
Background References
1. Zakharchenko O et al. A role of TGF 1 dependent 14-3-3s phosphorylation at Ser69 and Ser74 in the regulation of gene transcription, stemness and radioresistance. PLoS One 8:e65163 (2013).
2. Skibinski CG et al. Proteomic changes induced by effective chemopreventive ratios of n-3:n-6 fatty acids and tamoxifen against MNU-induced mammary cancer in the rat. Cancer Prev Res (Phila) 6:979-88 (2013).
Sequence Similarity
Belongs to the 14-3-3 family.
Tissue Specificity
Present mainly in tissues enriched in stratified squamous keratinizing epithelium.
Post-translational Modification
Ubiquitinated. Ubiquitination by RFFL induces proteasomal degradation and indirectly regulates p53/TP53 activation.