Fourteen-three-three protein (14-3-3)

Fourteen-three-three proteins (14-3-3) are a highly conserved family of regulatory scaffold proteins ubiquitously expressed in eukaryotic cells. The family comprises seven isoforms in humans (β, ε, γ, η, σ, τ, ζ), each about 30 kDa, typically functioning as homo- or heterodimers. They bind phosphorylated serine/threonine motifs in hundreds of partner proteins, thereby regulating diverse cellular processes such as signal transduction, cell cycle, apoptosis, and stress responses. 14-3-3 proteins act primarily by modulating the conformation, localization, stability, and interactions of their partners. Alterations in 14-3-3 function or expression are implicated in multiple diseases, notably cancer, neurodegenerative, cardiovascular, and psychiatric disorders, and their dysregulation can affect broad biological networks. While targeting 14-3-3 protein interactions has significant therapeutic potential, especially with small-molecule stabilizers or disruptors of PPIs, drug development is challenged by functional pleiotropy and redundancy among isoforms

Other names

14-3-3 protein familyYWHA proteinsTyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation proteinsSeven distinct human isoforms (β, ε, γ, η, σ, τ, ζ)sometimes also written as "fourteen-three-three proteins" or "14-3-3s"

Stabilization or disruption of 14-3-3/protein interactions (by small molecules, peptides, or natural products) Modulation of partner protein conformational state or localization by affecting 14-3-3 binding