Document Detail

The adenovirus E1A protein overrides the requirement for cellular ras in initiating DNA synthesis.
MedLine Citation:
PMID:  7813447     Owner:  NLM     Status:  MEDLINE    
The adenovirus E1A protein can induce cellular DNA synthesis in growth-arrested cells by interacting with the cellular protein p300 or pRb. In addition, serum- and growth factor-dependent cells require ras activity to initiate DNA synthesis and recently we have shown that Balb/c 3T3 cells can be blocked in either early or late G1 following microinjection of an anti-ras antibody. In this study, the E1A 243 amino acid protein is shown through microinjection not only to shorten the G0 to S phase interval but, what is more important, to override the inhibitory effects exerted by the anti-ras antibody in either early or late G1. Specifically, whether E1A is co-injected with anti-ras into quiescent cells or injected 18 h following a separate injection of anti-ras after serum stimulation, it efficiently induces cellular DNA synthesis in cells that would otherwise be blocked in G0/G1. Moreover, injection of a mutant form of E1A that can no longer associate with p300 is just as efficient as wild-type E1A in stimulating DNA synthesis in cells whose ras activity has been neutralized by anti-ras. The results presented here show that E1A is capable of overriding the requirement of cellular ras activity in promoting the entry of cells into S phase. Moreover, the results suggest the possibility that pRb and/or pRb-related proteins may function in a ras-dependent pathway that enables E1A to achieve this activity.
D W Stacey; S F Dobrowolski; A Piotrkowski; M L Harter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The EMBO journal     Volume:  13     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  1994 Dec 
Date Detail:
Created Date:  1995-02-03     Completed Date:  1995-02-03     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  6107-14     Citation Subset:  IM    
Department of Molecular Biology, Cleveland Clinic Foundation, OH 44195.
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MeSH Terms
3T3 Cells
Adenovirus E1A Proteins / immunology,  metabolism*
Antibodies, Monoclonal / pharmacology
Cell Cycle / drug effects,  physiology*
DNA / biosynthesis*
E1A-Associated p300 Protein
G0 Phase / physiology
G1 Phase / physiology
Mice, Inbred BALB C
Nuclear Proteins / metabolism
Proto-Oncogene Proteins p21(ras) / metabolism*
Retinoblastoma Protein / metabolism
S Phase / physiology
Transcription Factors / metabolism
Grant Support
Reg. No./Substance:
0/Adenovirus E1A Proteins; 0/Antibodies, Monoclonal; 0/Ep300 protein, mouse; 0/Nuclear Proteins; 0/Retinoblastoma Protein; 0/Trans-Activators; 0/Transcription Factors; 9007-49-2/DNA; EC p300 Protein; EC Proteins p21(ras)

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