The Establishment of a Hyperactive Structure Allows the Tumour Suppressor Protein p53 to Function through P-TEFb during Limited CDK9 Kinase Inhibition

摘要: CDK9 is the catalytic subunit of positive elongation factor b (P-TEFb) that controls transition RNA polymerase II (RNAPII) into elongation. inhibitors block mRNA synthesis and trigger activation stress-sensitive p53 protein. This in turn induces transcription CDKN1A (p21) other cell cycle control genes. It presently unclear if how circumvents a general P-TEFb-requirement when it activates its target Our investigations using panel specific reason for critical role also case direct inhibition kinase. At prototypic p21 gene, activator initially accumulates at pre-bound upstream enhancer followed—with significant delay—by de novo binding to secondary site within first intron p21. accompanied by recruitment RNAPII initiation machinery both elements. ChIP functional analyses prominent itself complexes PAF1c SEC involved pause control. appears strong potential facilitates gene situation global repression transcription. The data further underline fundamental importance class