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Am J Physiol Cell Physiol. 2004 Dec;287(6):C1541-6. Epub 2004 Aug 18.

Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21(Waf1/Cip1).

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  • 1Clinical Research Unit, University Hospital of Marburg, Baldingerstrasse, D-35033 Marburg, Germany. rgoeke@gmx.net

Abstract

We show that the recently discovered tumor suppressor pdcd4 represses the transcription of the mitosis-promoting factor cyclin-dependent kinase (CDK)1/cdc2 via upregulation of p21(Waf1/Cip1). p21(Waf1/Cip1) inhibits CDK4/6 and CDK2. Decrease of CDK4/6 and CDK2 enhances the binding of pRb to E2F/DP, which in turn together bind to and repress the cdc2 promoter. Upregulation of CDK1/cdc2 accompanied by a malignant change was previously reported in colon cancer. We show that expression of pdcd4 as an indirect suppressor of CDK1/cdc2 is lost in progressed carcinomas of lung, breast, colon, and prostate. Furthermore, it seems that localization and expression of pdcd4 directly correlate with tumor progression. Finally, the CDK1/cdc2 inhibitor roscovitine reduces the proliferation of several tumor cell lines, suggesting that inhibition of CDK1/cdc2 may be a useful strategy against malignant transformation. Therefore, pdcd4 might serve as a novel target for antineoplastic therapies.

PMID:
15317660
[PubMed - indexed for MEDLINE]
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