The EBV latent membrane protein, LMP1, is essential for EBV-induced B lymphocyte transformation and it is expressed in nasopharyngeal carcinoma and Hodgkins Disease. LMP1 is an integral membrane protein that has pleiotropic effects on B lymphocytes and epithelial cells, many of which are mediated by alterations in cellular gene expression. This proposal will elucidate the biochemical events that mediate signal transduction by LMP1. A functionally important domain of LMP1 interacts with members of the TRAF family of cytoplasmic proteins that are implicated in signalling from members of the tumor necrosis factor receptor family. The amino acid sequence of LMP1 that is involved in interactions with TRAF proteins will be identified and characterized in detail. Competitive inhibitors for the interactions will be designed and tested for their effects on LMP1 signalling and the growth of EBV transformed cells. LMP1 mutants that are compromised in their interactions with the TRAF proteins will be tested for their transforming properties. Downstream effectors of the TRAF signalling pathway will be identified using the yeast two hybrid.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA071705-03
Application #
2769878
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Wong, May
Project Start
1996-09-05
Project End
2001-08-31
Budget Start
1998-09-11
Budget End
1999-08-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115