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PMID: 7823921 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Modulation of p53-mediated transcriptional repression and apoptosis by the adenovirus E1B 19K protein.

Molecular and cellular biology ·Vol. 15 ·No. 2 ·1995-02-00 ·Pages 1060-70

Sabbatini P, Chiou SK, Rao L, White E

Abstract

BRK cell lines that stably express adenovirus E1A and a murine temperature-sensitive p53 undergo apoptosis when p53 assumes the wild-type conformation. Expression of the E1B 19,000-molecular-weight (19K) protein rescues cells from this p53-mediated apoptosis and diverts cells to a growth-arrested state. As p53 likely functions as a tumor suppressor by regulating transcription, the ability of the E1B 19K protein to regulate p53-mediated transactivation and transcriptional repression was investigated. In promoter-reporter assays the E1B 19K did not block p53-mediated transactivation but did alleviate p53-mediated transcriptional repression. E1B 19K expression permitted efficient transcriptional activation of the p21/WAF-1/cip-1 mRNA by p53, consistent with maintenance of the growth arrest function of p53. The E1B 19K protein is thereby unique among DNA virus-transforming proteins that target p53 for inactivation in that it selectively modulates the transcriptional properties of p53. The E1B 19K protein also rescued cells from apoptosis induced by inhibitors of transcription and protein synthesis. This suggests that cell death may result from the inhibition of expression of survival factors which function to maintain cell viability. p53 may induce apoptosis through generalized transcriptional repression. In turn, the E1B 19K protein may prevent p53-mediated apoptosis by alleviating p53-mediated transcriptional repression.

MeSH Terms
Adenovirus E1B Proteins/metabolism Animals Apoptosis Base Sequence Blotting, Northern Cell Division Cell Line Cell Survival Chloramphenicol O-Acetyltransferase/metabolism Gene Expression HeLa Cells Humans Kidney Kinetics Mice Plasmids Protein Conformation Rats Recombinant Proteins/metabolism Transcription, Genetic Transcriptional Activation Transfection Tumor Suppressor Protein p53/chemistry,metabolism
Chemicals
Adenovirus E1B Proteins Recombinant Proteins Tumor Suppressor Protein p53 Chloramphenicol O-Acetyltransferase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Sabbatini P
Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854.
Chiou S K
Rao L
White E
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.15.2.1060
Published
1995-02-00
Pages
1060-70
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC232006
Subset
IM
Grants
NCI NIH HHS · CA53370 · United States
NCI NIH HHS · CA60088 · United States
External Links
PubMed source DOI: 10.1128/MCB.15.2.1060 PMC Full Text View journal details
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