Overexpression of DRAM enhances p53‐dependent apoptosis

Cancer Medicine

Masahiro Takahashi¹  Yuichi Kakudo¹  Shin Takahashi¹  Yasuhiro Sakamoto¹  Shunsuke Kato¹ 

[1] Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Japan

关键词: Apoptosis;    DRAM;    p53;    super p53;   

DOI  :  10.1002/cam4.39

来源: Wiley

【 摘 要 】

Abstract

Tumor suppressor p53-dependent apoptosis is thought to be one of the most important tumor-suppressive mechanisms in human tumorigenesis. Till date, “super p53” mutants exhibiting more potent ability to induce apoptosis than wild-type p53 have been reported. These super p53s may provide a clue for development of novel therapeutic targets. However, the major mechanism underlying the super p53-dependent apoptosis remains unclear. To identify critical gene(s) in this mechanism, we performed a comprehensive and comparative expression analysis in p53-null Saos-2 cells with conditional expression of wild-type p53 and S121F, which was previously reported as a super p53 mutant. We identified damage-regulated autophagy modulator (DRAM) as one of the genes that were more upregulated by S121F than wild-type p53. Although knockdown of DRAM was not sufficient for reducing the ability of S121F to induce apoptosis, DRAM overexpression enhanced the ability in a wild-type p53-dependent manner. Here, we show that DRAM is an important gene for the enhancement of p53-dependent apoptosis. Additional analysis of the mechanism of super p53-dependent apoptosis may lead to the identification of novel drug targets for cancer therapy.

【 授权许可】

CC BY   
© 2012 The Authors. Cancer Medicine published by Blackwell Publishing Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.