Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ)

Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ, commonly referred to as 14-3-3 protein zeta/delta) is a highly conserved adapter protein that regulates numerous signal transduction pathways by binding to phosphorylated serine/threonine motifs on partner proteins[1][3][5]. It forms dimers that create a ligand-binding groove, which enables YWHAZ to modulate the activity, subcellular localization, and stability of diverse targets, including kinases, transcription factors, and cytoskeletal regulators[3][4][5]. YWHAZ is broadly involved in essential cellular functions such as apoptosis inhibition, cell cycle progression, protein trafficking, and cellular response to stress, frequently acting to promote cell survival and proliferation[1][3][4][5]. Overexpression or dysregulation of YWHAZ is implicated in the development and progression of multiple human diseases, notably various cancer types (where it contributes to chemoresistance, metastasis, and cell survival), neurodegenerative disorders (through tau protein interactions), inflammatory arthritis, and certain respiratory and infectious diseases[3][4][5]. Due to its hub role and broad function, YWHAZ is under investigation both as a prognostic biomarker and a potential—though challenging—therapeutic target[3][4][5].

Other names

14-3-3 protein zeta/delta14-3-3-zeta14-3-3 deltaKCIP-1Protein kinase C inhibitor protein 1Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, delta polypeptideYWHADHEL-S-3HEL-S-93HEL4POPCHAS

Drugs or research molecules typically act by disrupting the protein–protein interactions mediated by YWHAZ’s amphipathic binding groove or by modulating upstream kinases that control phosphorylation of YWHAZ-binding proteins[4][5].