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. 1997 Dec;71(12):9410–9416. doi: 10.1128/jvi.71.12.9410-9416.1997

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

Q Sheng 1, D Denis 1, M Ratnofsky 1, T M Roberts 1, J A DeCaprio 1, B Schaffhausen 1
PMCID: PMC230245  PMID: 9371601

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.

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Selected References

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