Virology Faculty Member - James DeCaprio

James DeCaprio

Associate Professor of Medicine

Dana Farber Cancer Institute
Mayer Bldg., Rm. 440
44 Binney St.
Boston, MA 02115
Tel: 617-632-3825
Fax: 617-582-8601
Email: james_decaprio@dfci.harvard.edu



The DeCaprio Laboratory has focused on the biological mechanisms of transformation by studying the SV40 large T antigen and the cellular factors and processes that T antigen perturbs. This work began with our demonstration that T antigen binds to the retinoblastoma tumor suppressor and continued with demonstration that the retinoblastoma regulates the G1 to S phase transition in the cell cycle. Since then, we demonstrated that T antigen inactivates the retinoblastoma related proteins, RBL1/p107 and RBL2/p130. We determined that T antigen contains a functional DNAJ heat shock domain that is required for inactivation of the RBL1 and RBL2. We have recently identified the human synMuvB complex in association with RBL1 and RBL2 and are pursuing its role in growth suppression.

We determined that large T antigen binds to CUL7, a novel Cullin protein, and that T antigen association is required for cellular transformation. We have identified several binding partners of CUL7 including PARC, FBXW8, p53 and GLMN. We determined that CUL7 and FBXW8 promote growth and that GLMN serves as an inhibitor of CUL7 function. CUL7 is mutated in the human dwarfism 3M syndrome and GLMN is mutated in the benign tumor syndrome of glomulovenous malformations. We are pursuing a biochemical and genetic analysis of the PARC-CUL7-FBXW8-GLMN complex to gain a more complete understanding of its role in growth control in mice and humans. In addition, we are studying how SV40 large T antigen perturbs the normal function of the CUL7 complex.

In addition to our study of viral transformation, our laboratory has studied the SV40 viral replication cycle. We determined that the large T antigen DNAJ domain provides a key role in SV40 virus replication. We determined that the C-terminus of T antigen provides a host range activity that specifically serves to increase viral gene expression. Current studies are focused at identifying additional cellular targets of T antigen and determining their role in transformation and replication.



Last Update: 10/22/2013



Publications

For a complete listing of publications click here.

 


 

Borger, D. R., and J. A. DeCaprio. 2006. Targeting of p300/CREB binding protein co activators by Simian Virus 40 is mediated through p53. J Virol 80:4292-4303.

Buchmann, A. M., J. R. Skaar, and J. A. DeCaprio. 2004. Activation of a DNA damage checkpoint response in a TAF1-defective cell line. Mol Cell Biol 24:5332-9.

Kasper, J. S., H. Kuwabara, T. Arai, S. H. Ali, and J. A. DeCaprio. 2005. Simian virus 40 large T antigen's association with the CUL7 SCF complex contributes to cellular transformation. J Virol 79:11685-92.

Litovchick, L., A. Chestukhin, and J. A. DeCaprio. 2004. Glycogen synthase kinase 3 phosphorylates RBL2/p130 during quiescence. Mol Cell Biol 24:8970-80.

Skaar, J. R., T. Arai, and J. A. DeCaprio. 2005. Dimerization of CUL7 and PARC is not required for all CUL7 functions and mouse development. Mol Cell Biol 25:5579-89.

Poulin, D. L., and J. A. Decaprio. 2006. The carboxyl-terminal domain of large T antigen rescues SV40 host range activity in trans independent of acetylation. Virology.

Poulin, D. L., and J. A. DeCaprio. 2006. Is there a role for SV40 in human cancer? J Clin Oncol in press.



© 2013 by the President and Fellows of Harvard College