p53-dependent repression of CDK4 translation in TGF-beta-induced G1 cell-cycle arrest.
- 15 January 1995
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 9 (2) , 204-217
- https://doi.org/10.1101/gad.9.2.204
Abstract
Transforming growth factor beta 1 (TGF-beta 1) can cause a cell-cycle arrest in G1. Inhibition of cyclin-dependent kinase 4 (cdk4) synthesis plays a significant role in the mechanism by which this cytokine causes G1 growth arrest. Deregulated expression of cdk4 confers resistance to TGF-beta 1. Here, we show that TGF-beta 1 down-regulates cdk4 expression by inhibiting its translation. Moreover, mutant p53 confers resistance to TGF-beta 1 by interfering with the down-regulation of cdk4 in response to the cytokine. In contrast, we demonstrate that wild-type p53 represses the translation of CDK4. Regulation of cdk4 synthesis by both p53 and TGF-beta 1 is mediated by the 5'-untranslated region of the CDK4 message. Thus, regulation of CDK4 translation may be involved in control of G1 progression by p53.Keywords
This publication has 80 references indexed in Scilit:
- p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21Published by Elsevier ,1994
- p21 is a universal inhibitor of cyclin kinasesNature, 1993
- Differential induction of transcriptionally active p53 following UV or lonizing radiation: Defects in chromosome instability syndromes?Cell, 1993
- WAF1, a potential mediator of p53 tumor suppressionCell, 1993
- Negative Regulation of G1 in Mammalian Cells: Inhibition of Cyclin E-Dependent Kinase by TGF-βScience, 1993
- Cloning of the Rat Cyclin-Dependent Kinase 4 cDNA: Implication in Proliferation-Dependent Expression in Rat TissuesBiochemical and Biophysical Research Communications, 1993
- Tumor-suppressor p53 and the cell cycleCurrent Opinion in Genetics & Development, 1993
- Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element.Genes & Development, 1992
- Identification of a growth suppression domain within the retinoblastoma gene product.Genes & Development, 1992
- The Transforming Growth Factor-beta FamilyAnnual Review of Cell Biology, 1990