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

14-3-3 proteins are a family of highly conserved regulatory adapter proteins that play a central role in cellular signaling by binding to a diverse range of phosphorylated client proteins (UniProt: P63104). These proteins, which include seven human isoforms (beta, gamma, epsilon, eta, sigma, theta, and zeta), function as molecular scaffolds that modulate the activity, subcellular localization, and stability of their binding partners (PMID: 30555144). By interacting with over 200 different clients, such as kinases, phosphatases, and transcription factors, 14-3-3 proteins regulate critical biological processes including the cell cycle, apoptosis, and signal transduction (Wikipedia: 14-3-3 protein). In many diseases, particularly cancer and neurodegeneration, the expression or interaction patterns of 14-3-3 proteins are significantly altered, contributing to pathological signaling (PMID: 29133758). Consequently, 14-3-3 proteins have emerged as attractive therapeutic targets, with drug development efforts focusing on small-molecule inhibitors or stabilizers that can specifically modulate protein-protein interactions to achieve therapeutic effects (PMID: 31430110).

Other names

Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation proteinYWHA family14-3-3 proteins14-3-3 adapter proteins

Modulation of protein-protein interactions (PPIs) by either inhibiting the binding of 14-3-3 to its client proteins or stabilizing the 14-3-3/client complex to alter downstream signaling pathways (PMID: 31430110).