The long term, overall goal of this research program is to elucidate the mechanism by which specific oncogenes contribute to the subversion of a cell from normal growth to oncogenically transformed behavior. Oncogene function will be investigated at the molecular, cellular and whole organism level. The research emphasis of component projects are as follow: Subproject 1. Shenk will study the mechanism by which the adenovirus type 5 E1B-55kD transforming protein can simultaneously inhibit accumulation of cellular mRNAs and stimulate accumulation of viral mRNAs, and he will study the mechanism whereby adenovirus type 9 can induce estrogen-dependent breast tumors in rats. Subproject 2. Cole will study the function of the c-myc protein in the control of normal and tumor cell growth, and he will investigate the possibility that other nuclear oncoproteins oncogenically transform cells by deregulating c-myc expression. Subproject 3. Broach will define the interactions between and among the numerous components of the signal transduction pathway in yeast in which RAS proteins (the yeast homolog of the mammalian ras oncoproteins) play a central role, and he will examine the role of a membrane-associated protein, Srv2p, in mediating RAS activation of adenylate cyclase. Subproject 4. Resh will study the biological roles of two postranslational modifications of the ras oncoprotein, farnesylation and palmitoylation; these studies will be carried out on both mammalian and yeast ras proteins. Subproject 5. Levine will test two hypotheses for the mechanism underlying the ability of p53 to negatively regulate cell growth and act as a tumor suppressor: first, he will explore the possibility that p53 is involved in events at the G1/S border of the cell cycle, and second, he will question whether p53 is involved in transcriptional regulation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA041086-07
Application #
3093843
Study Section
Special Emphasis Panel (SRC (I1))
Project Start
1986-07-01
Project End
1996-04-30
Budget Start
1992-05-01
Budget End
1993-04-30
Support Year
7
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Princeton University
Department
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
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