DF/HCC Program Affiliation

Cancer Cell Biology
Cancer Genetics

DF/HCC Associations

Director, Monoclonal Antibody
Member, Center Scientific Council

Research Abstract

This laboratory is focused on understanding the mechanisms of cellular transformation. In particular, we study how SV40 large T antigen (T Ag) is capable of inducing all of the cellular changes associated with oncogenic transformation. Cellular transformation by T Ag is dependent, at least in part, on inactivation of cellular tumor suppressers. Genetic analysis has led to identification of three transforming domains of T Ag: a C-terminal domain that binds the p53 tumor suppresser and the p300/CBP transcription coactivators; the LxCxE domain that binds the retinoblastoma (pRB) family of tumor suppressers, including pRB, p107 and p130 and an N-terminal domain that resembles the J domain found in the DnaJ/hsp40 family of molecular chaperones. The laboratory seeks to identify novel cellular targets of SV40 T Ag. We have identified a novel E3 ubiquitin ligase, CUL7/FBXW8, that binds to T Ag and appears to contribute to viral oncogenesis.

Publications

• Skaar JR, Florens L, Tsutsumi T, Arai T, Tron A, Swanson SK, Washburn MP, DeCaprio JA.PARC and CUL7 form atypical cullin RING ligase complexes.Cancer Res 2007 Mar 1;67(5):2006-14.
  17332328
• Poulin DL, DeCaprio JA.Is there a role for SV40 in human cancer?.J Clin Oncol 2006 Sep 10;24(26):4356-65.
  16963733
• Kasper JS, Arai T, Decaprio JA.A novel p53-binding domain in CUL7.Biochem Biophys Res Commun 2006 Jul 13.
  16875676
• Poulin DL, DeCaprio JA.The carboxyl-terminal domain of large T antigen rescues SV40 host range activity in trans independent of acetylation.Virology 2006 May 25;349(1):212-21.
  16510165
• Kasper JS, Kuwabara H, Arai T, Ali SH, DeCaprio JA.Simian virus 40 large T antigen's association with the CUL7 SCF complex contributes to cellular transformation.J Virol 2005 Sep;79(18):11685-92.
  16140746
• Skaar JR, Arai T, DeCaprio JA.Dimerization of CUL7 and PARC is not required for all CUL7 functions and mouse development.Mol Cell Biol 2005 Jul;25(13):5579-89.
  15964813
• Litovchick L, Chestukhin A, DeCaprio JA.Glycogen synthase kinase 3 phosphorylates RBL2/p130 during quiescence.Mol Cell Biol 2004 Oct;24(20):8970-80.
  15456871
• Buchmann AM, Skaar JR, DeCaprio JA.Activation of a DNA damage checkpoint response in a TAF1-defective cell line.Mol Cell Biol 2004 Jun;24(12):5332-9.
  15169897
• Arai T, Kasper JS, Skaar JR, Ali SH, Takahashi C, DeCaprio JA.Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis.Proc Natl Acad Sci U S A 2003 Aug 19;100(17):9855-60.
  12904573