The amino-terminal transforming region of simian virus 40 large T and small t antigens functions as a J domain

Mol Cell Biol. 1997 Aug;17(8):4761-73. doi: 10.1128/MCB.17.8.4761.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Animals
  • Antigens, Polyomavirus Transforming / genetics*
  • Antigens, Polyomavirus Transforming / metabolism
  • Antigens, Polyomavirus Transforming / physiology
  • Cell Line
  • Cell Transformation, Viral / genetics*
  • Conserved Sequence / genetics
  • Cyclins / genetics
  • Fibroblasts
  • Fungal Proteins / metabolism
  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / genetics
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Phosphoprotein Phosphatases / metabolism
  • Phosphoproteins / metabolism
  • Promoter Regions, Genetic / genetics
  • Proteins*
  • Rats
  • Retinoblastoma Protein / metabolism
  • Retinoblastoma-Like Protein p107
  • Retinoblastoma-Like Protein p130
  • Saccharomyces cerevisiae Proteins
  • Simian virus 40 / immunology*
  • Trans-Activators / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antigens, Polyomavirus Transforming
  • Cyclins
  • Fungal Proteins
  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Proteins
  • Rbl1 protein, mouse
  • Rbl2 protein, mouse
  • Rbl2 protein, rat
  • Retinoblastoma Protein
  • Retinoblastoma-Like Protein p107
  • Retinoblastoma-Like Protein p130
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • YDJ1 protein, S cerevisiae
  • Phosphoprotein Phosphatases
  • Adenosine Triphosphatases
  • SSA1 protein, S cerevisiae