1. CDK inhibitors selectively diminish cell cycle controlled activation of the histone H4 gene promoter by p220NPAT and HiNF-P.
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MITRA, PARTHA, GHULE, PRACHI N., VAN DER DEEN, MARGARETHA, MEDINA, RICARDO, RONG-LIN XIE, HOLMES, WILLIAM F., XIN YE, NAKAYAMA, KEIICHI I., HARPER, J. WADE, STEIN, JANET L., STEIN, GARY S., and VAN WIJNEN, ANDRE J.
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CYCLIN-dependent kinases , *PROTEIN kinases , *CELL cycle , *BIOLOGICAL rhythms , *CELL proliferation - Abstract
Cell cycle progression into S phase requires the induction of histone gene expression to package newly synthesized DNA as chromatin. Cyclin E stimulation of CDK2 at the Restriction point late in G1 controls both histone gene expression by the p220NPAT/HiNF-P pathway and initiation of DNA replication through the pRB/E2F pathway. The three CDK inhibitors (CKIs) p21CIP1/WAF1, p27KIP1, and p57KIP2 attenuate CDK2 activity. Here we find that γ-irradiation induces p21CIP1/WAF1 but not the other two CKIs, while reducing histone H4 mRNA levels but not histone H4 gene promoter activation by the p220NPAT/HiNF-P complex. We also show that p21CIP1/WAF1 is less effective than p27KIP1 and p57KIP2 in inhibiting the CDK2 dependent phosphorylation of p220NPAT at subnuclear foci and transcriptional activation of histone H4 genes. The greater effectiveness of p57KIP2 in blocking the p220NPAT/HiNF-P pathway is attributable in part to its ability to form a specific complex with p220NPAT that may suppress CDK2/cyclin E phosphorylation through direct substrate inhibition. We conclude that CKIs selectively control stimulation of the histone H4 gene promoter by the p220NPAT/HiNF-P complex. J. Cell. Physiol. 219: 438–448, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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