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Abstract
Grant Number: 5R37CA015751-29 Project Title: STRUCTURE AND FUNCTION OF SV40 NON-VIRION PROTEINS
PI Information: Name Title LIVINGSTON, DAVID M. david_livingston@dfci.harvard.edu PROFESSOR OF MEDICINE Abstract: Certain small and intermediate size DNA Tumor Viruses, such as the papovaviruses and the human adenoviruses, encode oncoproteins which deliver powerful signals that can seriously change the biology of mammalian cells. Among the outcomes is a state of neoplastic transformation, which can lead to tumorigenicity in a sutitable animal host. SV40 large T Ag and adenovirus E1A and two such oncoproteins, and their transforming functions are, in part, dependent upon their ability to interact with and perturb the functions of p300 and CBP, two large, closely related nuclear signal integrating and transformation suppressing proteins. In this application we will explore: i) the molecular relationships between loss of genetically defined primary murine fibroblasts; ii) the mechanisms which govern a newly discovered ability of p300/CBP to sustain mdm2-mediated p53 ubiquitination and turnover; and iii) the nature of the biochemical and biological functions of E1A/T/p53-associated p400, which turns out to be a complex of two polypeptides, TRRAP, a large C-terminal PI-3 kinase domain- containing protein, and a heretofore unrecognized member of the Swi/SNF family of chromatin remodeling proteins.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
protein structure function, simian virus 40, virus protein
Adenoviridae, cell cycle, cell growth regulation, fibroblast, oncoprotein, p53 gene /protein, phosphatidylinositol 3 kinase, ubiquitin, viral carcinogenesis, virus replication
gene targeting, immunochemistry, laboratory mouse, molecular cloning
Institution: DANA-FARBER CANCER INSTITUTE 44 BINNEY ST BOSTON, MA 02115 Fiscal Year: 2002 Department: Project Start: 22-SEP-1981 Project End: 30-JUN-2004 ICD: NATIONAL CANCER INSTITUTE IRG: VR
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