αB‐crystallin: A novel p53‐target gene required for p53‐dependent apoptosis

The p53 protein is a transcription factor that trans‐activates various genes in response to DNA‐damaging stress. To search for new p53‐target genes, we applied a cDNA microarray system using two independent p53‐inducible cell lines, followed by in silico analysis to detect p53 response elements. Here, we report on crystallin alpha B gene (CRYAB), which encodes αB‐crystallin, and is one of the genes directly trans‐activated by p53. We confirmed it is directly transcribed by p53 using promoter analysis, deletion reporter assay, ChIP assay and EMSA. αB‐crystallin is also upregulated in a p53‐dependent manner and binds to the DNA‐binding domain of p53. Overexpression of αB‐crystallin increased p53 protein and, in contrast, repression of αB‐crystallin decreased p53 protein. Interestingly, both overexpression and repression of αB‐crystallin reduced p53‐dependent apoptosis. In conclusion, we identified that αB‐crystallin was a novel p53‐target gene and required for p53‐dependent apoptosis using two independent p53‐inducible cell lines. This is the first report associating p53 directly with a heat shock protein through trans‐activation and physical interaction. (Cancer Sci 2009; 100: 2368–2375)