E1A induces phosphorylation of the retinoblastoma protein independently of direct physical association between the E1A and retinoblastoma products

Wang, H. G., Draetta, G., Moran, E. (August 1991) E1A induces phosphorylation of the retinoblastoma protein independently of direct physical association between the E1A and retinoblastoma products. Mol Cell Biol, 11 (8). pp. 4253-65. ISSN 0270-7306 (Print)0270-7306 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/1830128
DOI: 10.1128/MCB.11.8.4253

Abstract

We have studied the initial effects of adenovirus E1A expression on the retinoblastoma (RB) gene product in normal quiescent cells. Although binding of the E1A products to pRB could, in theory, make pRB phosphorylation unnecessary for cell cycle progression, we have found that the 12S wild-type E1A product is capable of inducing phosphorylation of pRB in normal quiescent cells. The induction of pRB phosphorylation correlates with E1A-mediated induction of p34cdc2 expression and kinase activity, consistent with the possibility that p34cdc2 is a pRB kinase. Expression of simian virus 40 T antigen induces similar effects. Induction of pRB phosphorylation is independent of the pRB binding activity of the E1A products; E1A domain 2 mutants do not bind detectable levels of pRB but remain competent to induce pRB phosphorylation and to activate cdc2 protein kinase expression and activity. Although the kinetics of induction are slower, domain 2 mutants induce wild-type levels of pRB phosphorylation and host cell DNA synthesis and yet fail to induce cell proliferation. These results imply that direct physical interaction between the RB and E1A products does not play a required role in the early stages of E1A-mediated cell cycle induction and that pRB phosphorylation is not, of itself, sufficient to allow quiescent cells to divide. These results suggest that the E1A products do not need to bind pRB in order to stimulate resting cells to enter the cell cycle. Indeed, a more important role of the RB binding activity of the E1A products may be to prevent dividing cells from returning to G0.

Item Type: Paper
Uncontrolled Keywords: Adenoviridae/genetics Adenovirus Early Proteins Animals CDC2 Protein Kinase/biosynthesis/genetics/metabolism Cell Line DNA Replication *Genes, Retinoblastoma *Genes, Viral Hydroxyurea/pharmacology Kinetics Mitosis Oncogene Proteins, Viral/*genetics/metabolism Phosphorylation Protein Kinases/metabolism Rats Rats, Inbred F344 Restriction Mapping Retinoblastoma Protein/*metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > cdc2
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation
CSHL Authors:
Communities: CSHL labs
Depositing User: Matt Covey
Date: August 1991
Date Deposited: 07 Jan 2016 21:08
Last Modified: 07 Jan 2016 21:08
PMCID: PMC361255
Related URLs:
URI: https://repository.cshl.edu/id/eprint/32069

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