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

Gou Watanabe, Shunsuke Kato, Hideyuki Nakata, Takanori Ishida, Noriaki Ohuchi, Chikashi Ishioka

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2368-2375
Number of pages8
JournalCancer science
Volume100
Issue number12
DOIs
Publication statusPublished - 2009 Dec

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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