MST1/STK4 Protein, Human (His)

MST1/STK4 protein is a stress-activated, pro-apoptotic kinase with diverse cellular functions, including a critical role in the Hippo signaling pathway. Following caspase-cleavage, MST1/STK4 enters the nucleus, inducing chromatin condensation and internucleosomal DNA fragmentation, contributing to apoptosis. In the Hippo pathway, MST1/STK4, along with its regulatory protein SAV1, forms a kinase cascade that phosphorylates and activates LATS1/2-MOB1 complex. This, in turn, phosphorylates and inactivates the YAP1 oncoprotein and WWTR1/TAZ, regulating genes involved in proliferation, cell death, and cell migration. MST1/STK4 is essential for repressing hepatocyte proliferation, inhibiting facultative adult liver stem cells, and preventing tumor formation. Additionally, it plays a role in histone modification during apoptosis, phosphorylates various substrates like FOXO3, MOBKL1A, MOBKL1B, RASSF2, TNNI3, and FOXO1, influencing diverse cellular processes such as transcription, cell death initiation, and signaling pathways like PKB/AKT1 and AR. Notably, MST1/STK4 acts as an inhibitor of PKB/AKT1, and its phosphorylation of SIRT1 promotes p53-dependent transcription and apoptosis in response to DNA damage. Furthermore, it intersects with PKB/AKT1 signaling to suppress AR activity by antagonizing the formation of AR-chromatin complexes.