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Cdk9 phosphorylates p53 on serine 392 independently of CKII
Author(s) -
Claudio Pier Paolo,
Cui Jianqi,
Ghafouri Mohammad,
Mariano Chiara,
White Martyn K.,
Safak Mahmut,
Sheffield Joel B.,
Giordano Antonio,
Khalili Kamel,
Amini Shohreh,
Sawaya Bassel E.
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20698
Subject(s) - cyclin dependent kinase 9 , rna polymerase ii , phosphorylation , casein kinase 2 , cyclin dependent kinase 2 , microbiology and biotechnology , biology , p tefb , protein kinase a , transcription (linguistics) , kinase , promoter , biochemistry , gene expression , gene , linguistics , philosophy
The tumor suppressor p53 is an important cellular protein, which controls cell cycle progression. Phosphorylation is one of the mechanisms by which p53 is regulated. Here we report the interaction of p53 with another key regulator, cdk9, which together with cyclin T1 forms the positive transcription elongation complex, p‐TEFb. This complex cooperates with the HIV‐1 Tat protein to cause the phosphorylation of the carboxyl terminal domain (CTD) of RNA polymerase II and this facilitates the elongation of HIV‐1 transcription. We demonstrate that cdk9 phosphorylates p53 on serine 392 through their direct physical interaction. Results from protein–protein interaction assays revealed that cdk9 interacts with the C‐terminal domain (aa 361–393) of p53, while p53 interacts with the N‐terminal domain of cdk9. Transfection and protein binding assays (EMSA and ChIP) demonstrated the ability of p53 to bind and activate the cdk9 promoter. Interestingly, cdk9 phosphorylates serine 392 of p53, which could be also phosphorylated by casein kinase II. Kinase assays demonstrated that cdk9 phosphorylates p53 independently of CKII. These studies demonstrate the existence of a feedback‐loop between p53 and cdk9, pinpointing a novel mechanism by which p53 regulates the basal transcriptional machinery. J. Cell. Physiol. 208: 602–612, 2006. © 2006 Wiley‐Liss, Inc.