14-3-3 protein family member (14-3-3)

The 14-3-3 protein family members are highly conserved, ubiquitously expressed eukaryotic adapter proteins that bind selectively to phosphoserine/phosphothreonine motifs in hundreds of client proteins, thereby regulating key cellular processes such as signal transduction, cell cycle progression, apoptosis, metabolism, and protein trafficking. The human genome encodes seven 14-3-3 isoforms (beta, gamma, epsilon, sigma, zeta, tau, and eta), which self-assemble as homo- or heterodimers. Each monomer is composed of nine alpha helices, forming a cup-shaped, amphipathic groove for ligand binding. Through their scaffold function, 14-3-3 proteins control the subcellular localization, stability, and/or activity of their partners. Dysregulation of 14-3-3 proteins has been implicated in cancer, neurodegenerative diseases, cardiovascular disorders, and more. While they are recognized as attractive therapeutic targets, direct pharmacological modulation remains challenging due to their structural adaptability, essential cellular roles, and isoform redundancy.

Other names

14-3-3 proteinYWHA protein family (YWHA is the gene prefix, e.g., YWHAZ, YWHAG, etc.)14-3-3 beta, gamma, epsilon, sigma, zeta, tau, eta (referring to the 7 human isoforms)Protein kinase C inhibitor protein 1 (historical context)Phosphoserine/phosphothreonine-binding protein

Modulation (inhibition or stabilization) of 14-3-3 interaction with binding partners, affecting phosphorylation-dependent signaling Disrupts/adapts protein-protein interactions that control target protein localization, stability, and activity