14-3-3 protein sigma (14-3-3σ)

14-3-3 protein sigma (SFN, also referred to as Stratifin) is a member of the highly conserved 14-3-3 protein family, which functions primarily as an adapter or scaffold protein capable of binding phosphorylated serine- or threonine-containing motifs on a wide array of client proteins. 14-3-3σ is especially recognized for its role in cell cycle arrest at the G2/M checkpoint in response to DNA damage, acting as a tumor suppressor in various epithelial tissues by sequestering key regulatory proteins in the cytoplasm and preventing aberrant mitotic entry. It also participates in the maintenance of desmosomal junctions in epithelial cells by capturing PKP3, and its loss or hypermethylation is frequently observed in a variety of carcinomas. Its involvement in numerous cellular signaling pathways underlies its potential as a therapeutic target and biomarker, but the functional redundancy and complexity within the 14-3-3 family present significant therapeutic challenges.

Other names

StratifinSFNHME1YWHAS14-3-3 sigma14-3-3σ

Modulates protein–protein interactions by binding to phosphorylated serine/threonine motifs on client proteins, influencing their stability, localization, and function. Functions as a scaffold, occluding or exposing interaction motifs to control downstream signaling. Regulates cytoplasmic sequestration of specific proteins (e.g., Cdc25C, PKP3), thereby modulating cell cycle and adhesion.