Abstract
Mutations in the p53 tumor suppressor gene occur in more than 50% of human cancers. In response to various cellular stresses, such as DNA damage, the p53 protein rapidly accumulates by posttranscriptional mechanism(s) and activates the expression of genes that play a major role in cellular responses leading to cell cycle arrest, DNA repair and apoptosis as a transcriptional activator. In particular, the induction of apoptosis is considered to be an important function in tumor suppression by p53. Recently, two BH3-only members of the Bcl-2 family, Noxa and PUMA, have been identified as p53 target genes1,2. Furthermore, the analysis of mice doubly deficient in multidomain Bcl-2 family proteins, Bax and Bak, revealed that apoptosis induced by the BH3-only protein is completely dependent on Bax and Bak3. More recently, it was demonstrated using gene knockout mice4,5 that Noxa and PUMA function as the effectors of p53-induced apoptosis. These analyses revealed that p53-induced apoptosis is regulated by these Bcl-2 family proteins. In this photogravure, the regulation of these Bcl-2 family proteins in p53-induced apoptosis was visualized by fluorescent protein fusion and immune fluorescence methods.
