alphaB-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 alphaB-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. alphaB-crystallin is also upregulated in a p53-dependent manner and binds to the DNA-binding domain of p53. Overexpression of alphaB-crystallin increased p53 protein and, in contrast, repression of alphaB-crystallin decreased p53 protein. Interestingly, both overexpression and repression of alphaB-crystallin reduced p53-dependent apoptosis. In conclusion, we identified that alphaB-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.
Department of Clinical Oncology, Research Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Gou
G
Watanabe
Shunsuke
S
Kato
Hideyuki
H
Nakata
Takanori
T
Ishida
Noriaki
N
Ohuchi
Chikashi
C
Ishioka
D017209:Apoptosis; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000502:physiology*
C059215:CRYAB protein, human; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D038203:alpha-Crystallin B Chain; D004247:DNA