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The amino-terminal transforming region of simian virus 40 large T and small t antigens functions as a J domain.
Srinivasan, A; McClellan, A J; Vartikar, J; Marks, I; Cantalupo, P; Li, Y; Whyte, P; Rundell, K; Brodsky, J L; Pipas, J M.
Afiliação
  • Srinivasan A; Department of Biological Sciences, University of Pittsburgh, Pennsylvania 15260, USA.
Mol Cell Biol ; 17(8): 4761-73, 1997 Aug.
Article em En | MEDLINE | ID: mdl-9234732
Simian virus 40 (SV40) encodes two proteins, large T antigen and small t antigen that contribute to virus-induced tumorigenesis. Both proteins act by targeting key cellular regulatory proteins and altering their function. Known targets of the 708-amino-acid large T antigen include the three members of the retinoblastoma protein family (pRb, p107, and p130), members of the CBP family of transcriptional adapter proteins (cap-binding protein [CBP], p300, and p400), and the tumor suppressor p53. Small t antigen alters the activity of phosphatase pp2A and transactivates the cyclin A promoter. The first 82 amino acids of large T antigen and small t antigen are identical, and genetic experiments suggest that an additional target(s) important for transformation interacts with these sequences. This region contains a motif similar to the J domain, a conserved sequence found in the DnaJ family of molecular chaperones. We show here that mutations within the J domain abrogate the ability of large T antigen to transform mammalian cells. To examine whether a purified 136-amino-acid fragment from the T antigen amino terminus acts as a DnaJ-like chaperone, we investigated whether this fragment stimulates the ATPase activity of two hsc70s and discovered that ATP hydrolysis is stimulated four- to ninefold. In addition, ATPase-defective mutants of full-length T antigen, as well as wild-type small t antigen, stimulated the ATPase activity of hsc70. T antigen derivatives were also able to release an unfolded polypeptide substrate from an hsc70, an activity common to DnaJ chaperones. Because the J domain of T antigen plays essential roles in viral DNA replication, transcriptional control, virion assembly, and tumorigenesis, we conclude that this region may chaperone the rearrangement of multiprotein complexes.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas / Transformação Celular Viral / Antígenos Transformantes de Poliomavirus / Vírus 40 dos Símios Limite: Animals Idioma: En Ano de publicação: 1997 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas / Transformação Celular Viral / Antígenos Transformantes de Poliomavirus / Vírus 40 dos Símios Limite: Animals Idioma: En Ano de publicação: 1997 Tipo de documento: Article