-Review-

p53 Biological Network: At the Crossroads of the Cellular-Stress Response Pathway and Molecular Carcinogenesis

S. Perwez Hussain and Cutis C. Harris

Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, USA

p53 as a key molecular node in the stress response pathway, including inflammation. p53 is involved in several critical pathways including cell cycle arrest, apoptosis, DNA repair, and cellular senescence, which are essential for normal cellular homeostasis and maintaining genome integrity. The alteration of the TP53 gene or posttranslational modification in the p53 protein can alter its response to cellular stress. The molecular archaeology of the TP53 mutation spectrum generates hypotheses concerning the etiology and molecular pathogenesis of human cancer. The spectrum of somatic mutations in the TP53 gene implicates environmental carcinogens, and both endogenous agents and processes in the etiology of human cancer.

J Nippon Med Sch 2006; 73: 54-64

Keywords
p53, nitric oxide, inflammation, cancer

Correspondence to
Curtis C. Harris, MD, Chief, Laboratory of Human Carcinogenesis, Bldg. 37, Room 3068 National Cancer Institute, NIH 37 Convent Dr. Bethesda, MD 20892-4255, USA
Curtis_Harris@nih.gov

Received, January 24, 2006
Accepted, February 22, 2006