The retinoblastoma protein is essential for cyclin A repression in quiescent cells

Oncogene
A PhilipsJ M Blanchard

Abstract

Cyclin A is a positive regulatory component of kinases required for the progression through S phase and for the transition between the G2 and M phases of the cell division cycle. Previous studies have demonstrated that the promoter of its gene is under transcriptional repression in quiescent cells. Whereas the DNA sequences mediating this effect have been clearly delineated, the nature of the proteins acting in trans is still debated. Indirect observations suggest the involvement of proteins related to the retinoblastoma tumor suppressor protein (pRb). However, the precise role of these proteins has been difficult to assess, since most experiments designed to analyse their function have been carried out in transformed cell lines. Nevertheless, a current model has emerged whereby the role of the p130 protein would be restricted to resting and early G1 cells and p107, absent in quiescent cells, would be involved later in the control of the G1/S transition, whilst pRb would be effective throughout the cell cycle. We show here that cyclin A transcriptional inhibition is relieved in primary fibroblasts from pRb(-/-) embryos and not in fibroblasts from p13O(-/-), p107(-/-) or even p130(-/-)/p107(-/-) double mutant embryos. This sugge...Continue Reading

Citations

Jul 2, 2011·Journal of Neuro-oncology·Alexander KofmanRoger Abounader
Jun 20, 2001·Journal of Virology·S SchüchnerE Wintersberger
Jul 5, 2001·Molecular and Cellular Biology·S AdachiJ M Sedivy
Apr 3, 2001·Molecular and Cellular Biology·L FajasM L Vignais
Dec 3, 2003·Molecular and Cellular Biology·Michela A TessariGuidalberto Manfioletti
May 7, 1999·Environmental Health Perspectives·R E ShackelfordR S Paules
Jul 8, 2000·Proceedings of the National Academy of Sciences of the United States of America·M W StrobeckE S Knudsen
Apr 20, 2005·Oncogene·David Cobrinik
Feb 1, 2005·Virus Research·G Joan GrindlayVincent O'Brien
May 25, 2002·Experimental Cell Research·Steven P AngusErik S Knudsen
Sep 27, 2003·Expert Review of Molecular Diagnostics·Amber YasmeenCarsten Müller-Tidow
Dec 22, 1999·Oncogene·A PhilipsJ M Blanchard
Sep 17, 1999·The Journal of Biological Chemistry·K E KnudsenE S Knudsen
Aug 24, 1999·Molecular and Cellular Biology·E VigoK Helin

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