[Frontiers in Bioscience 16, 749-758, January 1, 2011]

Micromanagement of the mitochondrial apoptotic pathway by p53

Vijay Walia1, Smita Kakar2, Randolph Elble1

1Department of Pharmacology and Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, Illinois 62794, 1Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 50011


1. Abstract
2. Introduction
3. Modulation of apoptosis by the Bcl-2 family
4. Inhibition of Bcl-2 and activation of Bax by translocation of p53 to mitochondria
5. Physical interaction of p53 with Bcl-2 family proteins
6. Modulators of p53 mitochondrial homing
7. Regulation of other pro-apoptotic mitochondrial proteins by p53: VDAC and CLIC4
8. Future directions
9. Acknowledgements
10. References


It is now well established that p53 is the primary arbiter of stress-response and the principal barrier to neoplastic processes at the cellular level. Perhaps the most potent weapon in p53's tumor suppressive arsenal is apoptosis, enacted as a last resort when all other remedies are exhausted. Initially, the mechanism was thought to be simply activation or repression of Bcl-2 family members by p53. More recently, evidence of a more rapid pathway emerged whereby p53 physically interacts with Bcl-2 family members to tip the balance toward apoptosis. This review details the multiple levels of regulation of mitochondrially-directed apoptosis by p53, including recent findings of how p53 translocation is regulated.