The impact of p53 on numerous aspects of normal and pathophysiological contexts is apparent from both in vitro and in vivo studies. Literature supports p53 is a critical regulator of cell cycle inhibition, genomic stability and apoptosis inclusive of most cell and tissue types. It is clear that p53 functions as a transcription factor to regulate the above effects and combined structure/mutation studies demonstrate the DNA binding and proline-rich domains of p53 are crucial to many of its protective effects in vertebrates. However, increasing evidence suggests p53 also controls apoptosis in a transcription-independent route. The goal of this research proposal is to explore the central mechanisms by which p53 can induce apoptosis in a transcription-independent manner using several novel in vitro and in vivo models. This work will be done in a unique cell-free system developed by our laboratory, several cell lines of diverse origin, and in primary cells from a recently generated knock-in mouse. Efforts will focus on the role of pro-apoptotic Bcl-2 family members in the permeabilization of the mitochondrial outer membrane and how p53 regulates this process.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA101444-02
Application #
6793988
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Lohrey, Nancy
Project Start
2003-08-16
Project End
2006-08-15
Budget Start
2004-08-16
Budget End
2005-08-15
Support Year
2
Fiscal Year
2004
Total Cost
$47,296
Indirect Cost
Name
La Jolla Institute
Department
Type
DUNS #
603880287
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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