14-3-3 gamma isoform (also known as tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma polypeptide) is encoded by the YWHAG gene in humans and is induced by growth factors in human vascular smooth muscle cells. It is also highly expressed in skeletal and heart muscles, suggesting an important role in muscle tissue. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways. 14-3-3 gamma mediates Cdc25A proteolysis to block premature mitotic entry after DNA damage. 14-3-3 gamma mediates the interaction between Chk1 and Cdc25A; this complex has an essential function in Cdc25A phosphorylation and degradation to block premature mitotic entry after DNA damage. Increased expression of 14-3-3 gamma in lung cancer coincides with loss of functional p53, possibly in a cooperative manner promoting genomic instability. Also, during cell cycle, 14-3-3 gamma protects p21, a cyclin-dependent kinase inhibitor, from degradation mediated by the p53 suppressor MDMX, which may account for elevation of p21 levels independent of p53 and in response to DNA damage. Elevated expression of 14-3-3 gamma in human hepatocellular carcinoma predicts extrahepatic metastasis and worse survival, thus making this protein a candidate biomarker and a potential target for novel therapies against the disease.
Jiyao W et al.(2023). "The conserved domain database in 2023.",