Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine ( , ). Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection ( ). May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response ( ). During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage ( ). Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation . Phosphorylates a number of DNA repair proteins in response to DNA damage, such as MDC1, RAD9A, RAD51 and HTATSF1, promoting their recruitment to DNA damage sites (  , ). Can also negatively regulate apoptosis (, ). Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3 ( ). Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8 ( ). Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV ( ). Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB ( ). Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function . Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1 . Acts as an ectokinase that phosphorylates several extracellular proteins ( ). During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV ( ).
Subcellular locations: Nucleus, Cytoplasm
Interaction with SIRT6 prevents translocation into the nucleus.