A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1

Phosphorylation of the human p53 protein at Ser-392 has been shown to be re sponsive to UV but not gamma irradiation. Here we describe identification a nd purification of a mammalian UV-activated protein kinase complex that pho sphorylates Ser-392 of p53 in vitro. This kinase complex contains casein ki nase 2 (CK2) and the chromatin transcriptional elongation factor FACT (a he terodimer of hSpt16 and SSRP1). In vitro studies show that FACT alters the specificity of CK2 in the complex such that it selectively phosphorylates p 53 over other substrates including casein. In addition, phosphorylation by the kinase complex enhances p53 activity. These results thus provide a pote ntial mechanism for p53 activation by UV irradiation.