期刊
CELL CYCLE
卷 7, 期 19, 页码 3056-3061出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.7.19.6751
关键词
Bcl-2; cancer; GFP-LC3; human colon carcinoma HCT 116 cells; MDM2; p53 hot-spot mutations
类别
资金
- EU
- Institut National contre le Cancer (INCa)
- CONICYT, Chile
- Cancerfonden
- Swedish Research Council
- EMBO
- Ligue Nationale contre le Cancer (equipe labellisee)
- European Commission
- Agence Nationale pour la Recherche
- Canceropole Ile-de-France
The knockout, knockdown or chemical inhibition of p53 stimulates autophagy. Moreover, autophagy-inducing stimuli such as nutrient depletion, rapamycin or lithium cause the depletion of cytoplasmic p53, which in turn is required for the induction of autophagy. Here, we show that retransfection of p53(-/-) HCT 116 colon carcinoma cells with wild type p53 decreases autophagy down to baseline levels. Surprisingly, one third among a panel of 22 cancer-associated p53 single amino acid mutants also inhibited autophagy when transfected into p53(-/-) cells. Those variants of p53 that preferentially localize to the cytoplasm effectively repressed autophagy, whereas p53 mutants that display a prominently nuclear distribution failed to inhibit autophagy. The investigation of a series of deletion mutants revealed that removal of the DNA-binding domain from p53 fails to interfere with its role in the regulation of autophagy. Altogether, these results identify the cytoplasmic localization of p53 as the most important feature for p53-mediated autophagy inhibition. Moreover, the structural requirements for the two biological activities of extranuclear p53, namely induction of apoptosis and inhibition of autophagy, are manifestly different.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据