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PMID: 9371601 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The DnaJ domain of polyomavirus large T antigen is required to regulate Rb family tumor suppressor function.

Journal of virology ·Vol. 71 ·No. 12 ·1997-12-00 ·Pages 9410-6

Sheng Q, Denis D, Ratnofsky M, Roberts TM, DeCaprio JA, Schaffhausen B

Abstract

Tumor suppressors of the retinoblastoma susceptibility gene family regulate cell growth and differentiation. Polyomavirus large T antigens (large T) bind Rb family members and block their function. Mutations of large T sequences conserved with the DnaJ family affect large T binding to a cellular DnaK, heat shock protein 70. The same mutations abolish large T activation of E2F-containing promoters and Rb binding-dependent large T activation of cell cycle progression. Cotransfection of a cellular DnaJ domain blocks wild-type large T action, showing that the connection between the chaperone system and tumor suppressors is direct. Although they are inactive in assays dependent on Rb family binding, mutants in the J region retain the ability to associate with pRb, p107, and p130. This suggests that binding of Rb family members by large T is not sufficient for their inactivation and that a functional J domain is required as well. This work connects the DnaJ and DnaK molecular chaperones to regulation of tumor suppressors by polyomavirus large T.

MeSH Terms
3T3 Cells Amino Acid Sequence Animals Antigens, Polyomavirus Transforming/chemistry,genetics,metabolism Binding Sites Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins E2F Transcription Factors HSP40 Heat-Shock Proteins Heat-Shock Proteins/chemistry,metabolism Humans Mice Molecular Sequence Data Mutagenesis Nuclear Proteins/genetics,metabolism Phosphoproteins/genetics,metabolism Proteins Repressor Proteins/genetics,metabolism Retinoblastoma Protein/genetics,metabolism Retinoblastoma-Binding Protein 1 Retinoblastoma-Like Protein p107 Retinoblastoma-Like Protein p130 Sequence Homology, Amino Acid Transcription Factor DP1 Transcription Factors/genetics Transcriptional Activation
Chemicals
Antigens, Polyomavirus Transforming Arid4a protein, mouse Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins E2F Transcription Factors HSP40 Heat-Shock Proteins Heat-Shock Proteins Nuclear Proteins Phosphoproteins Proteins RBL1 protein, human RBL2 protein, human Rbl1 protein, mouse Rbl2 protein, mouse Repressor Proteins Retinoblastoma Protein Retinoblastoma-Binding Protein 1 Retinoblastoma-Like Protein p107 Retinoblastoma-Like Protein p130 Transcription Factor DP1 Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Sheng Q
Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Denis D
Ratnofsky M
Roberts T M
DeCaprio J A
Schaffhausen B
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.71.12.9410-9416.1997
Published
1997-12-00
Pages
9410-6
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC230245
Subset
IM
Grants
NCI NIH HHS · R01 CA034722 · United States
NCI NIH HHS · CA32222 · United States
NCI NIH HHS · CA34722 · United States
NCI NIH HHS · CA50661 · United States
External Links
PubMed source DOI: 10.1128/JVI.71.12.9410-9416.1997 PMC Full Text View journal details
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