The goal of this program is to understand the function and regulation of nuclear oncogenes. Recent findings indicate that nuclear oncoproteins are the final targets and mediators of signal transduction pathways activated by growth factors and transforming oncoproteins that act in the cell surface or the cytoplasm. By modulating the expression and activity of nuclear oncoproteins, that act as sequence specific transcription factors, these agents affect the expression of genes involved in cell proliferation, migration, invasiveness and deposition of extracellular matrix. Much of this regulation occurs by changes in the phosphorylation level of nuclear oncoproteins. This program will focus on studying two transcription factors whose deregulated activation can lead to malignant transformation: AP-1 (jun/Fos) and E2A-Pbx1. While AP-1 is a primary regulator of genes involved in the control of cell proliferation, E2A- Pbx1 is likely to function by affecting the expression of other regulatory genes, such as jun and fos. To achieve its goals the program includes four projects that will investigate: 1) the function and regulation of the c-jun protooncogene; 2) the regulation of AP-1 activity by TGFbeta; 3) the mitogenic function of the vAb1 tyrosine kinase, and 4) the biochemical regulation and transforming mechanisms of E2A-Pbx1. A common theme shared by all of these projects is the investigation of how positively- and negatively-acting growth regulatory pathways affect the activities of nuclear oncoproteins by post-translational control mechanisms involving either protein phosphorylation or interactions with other proteins.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
3P01CA050528-07S2
Application #
2563938
Study Section
Special Emphasis Panel (SRC (M1))
Project Start
1989-09-08
Project End
1998-01-31
Budget Start
1996-02-01
Budget End
1998-01-31
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Pharmacology
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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White, F C; Benehacene, A; Scheele, J S et al. (1997) VEGF mRNA is stabilized by ras and tyrosine kinase oncogenes, as well as by UV radiation--evidence for divergent stabilization pathways. Growth Factors 14:199-212
Knoepfler, P S; Kamps, M P (1997) The highest affinity DNA element bound by Pbx complexes in t(1;19) leukemic cells fails to mediate cooperative DNA-binding or cooperative transactivation by E2a-Pbx1 and class I Hox proteins - evidence for selective targetting of E2a-Pbx1 to a subset of P Oncogene 14:2521-31
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