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Abstract

Grant Number:	2R37CA053394-12
Project Title:	Mechanism of action of the v-erb A oncogene of AEV.

PI Information:	Name	Email	Title
	PRIVALSKY, MARTIN L.	mlprivalsky@ucdavis.edu	PROFESSOR OF MICROBIOLOGY

Abstract: DESCRIPTION (provided by applicant): The v-erb A oncogene potentiates erythroid transformation and alters the growth properties of fibroblasts. V-erb A is a virus transduced, aberrant copy of a gene for a thyroid hormone receptor. Thyroid hormone receptors (TRs) are ligand-regulated transcription factors, and belong to a larger family of nuclear receptors that play crucial roles in metazoan homeostasis, differentiation, and neoplasia. The v-Erb A protein acts as a transcriptional repressor, inhibiting expression of genes normally activated by TRs and by the closely related retinoic acid receptors (RARs). Therefore, v-erb A has been proposed as a prototype of a novel class of oncogene, acting in cancer as a dominant-negative allele. Similar dominant-negative mutants of nuclear receptors, such as PML-RAR, play important roles in human endocrine disease and cancers. We wish to understand the mechanism of action of the v-erb A oncogene, to relate its role in viral neoplasia to events in normal differentiation, and to use v-erb A as a model to provide new insights into human diseases. A. We will identify v-Erb A and PML-RAR target genes. B. We will determine how v-Erb A represses target gene expression once bound to a target DNA. C. We will determine how v-Erb A function is altered by other signal transduction pathways operative in the erythroleukemic cell. D. V-Erb A will be used as a model to improve our understanding of the actions of the aberrant nuclear receptors involved in human disease. Due to its derivation from a nuclear hormone receptor, v-erb A is one of the most experimentally accessible oncogenes, and holds unusual potential for understanding both neoplasia and the actions of nuclear hormone receptors in the normal organism.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
avian type C retrovirus group, gene induction /repression, hormone receptor, neoplastic transformation, nuclear receptor, oncogene, oncoprotein, thyroid hormone, transcription factor, viral carcinogenesis, virus genetics
erythroleukemia, gene mutation, oncogenic virus, protooncogene, thyroid hormone binding protein
chicken, fluorescence microscopy, gel mobility shift assay, immunoprecipitation, northern blotting, polymerase chain reaction

Institution:	UNIVERSITY OF CALIFORNIA DAVIS
	OFFICE OF RESEARCH - SPONSORED PROGRAMS
	DAVIS, CA 95618
Fiscal Year:	2003
Department:	BIOLOGICAL SCIENCES
Project Start:	07-FEB-1994
Project End:	30-APR-2008
ICD:	NATIONAL CANCER INSTITUTE
IRG:	VR

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