Identification of dihydropyrimidinase-related protein 4 as a novel target of the p53 tumor suppressor in the apoptotic response to DNA damage
✍ Scribed by Junko Kimura; Takuya Kudoh; Yoshio Miki; Kiyotsugu Yoshida
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- French
- Weight
- 690 KB
- Volume
- 128
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
The p53 tumor suppressor gene, which is frequently mutated in a wide variety of tumors, plays an important role in maintaining genomic integrity. Following genotoxic insults, the protein level of p53 is increased, and p53 functions as a sequence‐specific transcription factor that regulates the expression of downstream target genes required for cell cycle arrest, DNA repair or apoptosis. However, the mechanism for p53‐inducible apoptosis remains largely unclear. To search novel downstream targets of p53 on apoptosis, we had carried out microarray analysis. We identified dihydropyrimidinase‐related protein (DPYSL) 4 gene, which was upregulated by overexpressing p53 in p53‐deficient cells. Both mRNA and protein expressions of DPYSL4 were specifically induced by anticancer agents in p53‐proficient cells. Further analyses demonstrated that DPYSL4 was a direct target for p53. We also found that genotoxic‐induced apoptosis was repressed in cells silenced for DPYSL4. These findings indicate that DPYSL4 is a novel apoptosis‐inducible factor controlled by p53 in response to DNA damage.