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PMID: 10891510 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Species-specific elements in the large T-antigen J domain are required for cellular transformation and DNA replication by simian virus 40.

Molecular and cellular biology ·Vol. 20 ·No. 15 ·2000-08-00 ·Pages 5749-57

Sullivan CS, Tremblay JD, Fewell SW, Lewis JA, Brodsky JL, Pipas JM

Abstract

The J domain of simian virus 40 (SV40) large T antigen is required for efficient DNA replication and transformation. Despite previous reports demonstrating the promiscuity of J domains in heterologous systems, results presented here show the requirement for specific J-domain sequences in SV40 large-T-antigen-mediated activities. In particular, chimeric-T-antigen constructs in which the SV40 T-antigen J domain was replaced with that from the yeast Ydj1p or Escherichia coli DnaJ proteins failed to replicate in BSC40 cells and did not transform REF52 cells. However, T antigen containing the JC virus J domain was functional in these assays, although it was less efficient than the wild type. The inability of some large-T-antigen chimeras to promote DNA replication and elicit cellular transformation was not due to a failure to interact with hsc70, since a nonfunctional chimera, containing the DnaJ J domain, bound hsc70. However, this nonfunctional chimeric T antigen was reduced in its ability to stimulate hsc70 ATPase activity and unable to liberate E2F from p130, indicating that transcriptional activation of factors required for cell growth and DNA replication may be compromised. Our data suggest that the T-antigen J domain harbors species-specific elements required for viral activities in vivo.

MeSH Terms
Amino Acid Sequence Animals Antigens, Viral, Tumor/physiology Bacterial Proteins/genetics,metabolism Binding Sites Carrier Proteins Cell Cycle Proteins Cell Transformation, Viral DNA Replication DNA-Binding Proteins E2F Transcription Factors Escherichia coli Proteins Fungal Proteins/genetics,metabolism HSP40 Heat-Shock Proteins HSP70 Heat-Shock Proteins/genetics,metabolism Heat-Shock Proteins/genetics,metabolism JC Virus/immunology Mammals Molecular Sequence Data Phosphoproteins/metabolism Proteins Recombinant Proteins/genetics,metabolism Retinoblastoma-Binding Protein 1 Retinoblastoma-Like Protein p130 Saccharomyces cerevisiae Proteins Simian virus 40/immunology,pathogenicity Species Specificity Transcription Factor DP1 Transcription Factors/metabolism Virus Replication
Chemicals
Antigens, Viral, Tumor Bacterial Proteins Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins DnaJ protein, E coli E2F Transcription Factors Escherichia coli Proteins Fungal Proteins HSP40 Heat-Shock Proteins HSP70 Heat-Shock Proteins Heat-Shock Proteins Phosphoproteins Proteins Recombinant Proteins Retinoblastoma-Binding Protein 1 Retinoblastoma-Like Protein p130 Saccharomyces cerevisiae Proteins Transcription Factor DP1 Transcription Factors YDJ1 protein, S cerevisiae
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Sullivan C S
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Tremblay J D
Fewell S W
Lewis J A
Brodsky J L
Pipas J M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.15.5749-5757.2000
Published
2000-08-00
Pages
5749-57
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC86052
Subset
IM
Grants
NCI NIH HHS · R01 CA040586 · United States
NCI NIH HHS · CA40586 · United States
External Links
PubMed source DOI: 10.1128/MCB.20.15.5749-5757.2000 PMC Full Text View journal details
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