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

AUTOR(ES)

Sheng, Q

RESUMO

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.

Documentos Relacionados

• J Domain-Independent Regulation of the Rb Family by Polyomavirus Large T Antigen
• The J Domain of Simian Virus 40 Large T Antigen Is Required To Functionally Inactivate RB Family Proteins
• Effect on Polyomavirus T-Antigen Function of Mutations in a Conserved Leucine-Rich Segment of the DnaJ Domain
• Legionella dumoffii DjlA, a Member of the DnaJ Family, Is Required for Intracellular Growth
• The T/t common exon of simian virus 40, JC, and BK polyomavirus T antigens can functionally replace the J-domain of the Escherichia coli DnaJ molecular chaperone