.png){kind=icon}
返回
Activating p53 function by targeting RLIP
.png){kind=icon}
OA
AI
DOI：10.1016/j.bbcan.2021.188512.png)
.png){kind=icon}
.png){kind=icon}
分享.png){kind=icon}
收藏
摘要
En 中文
Aberrations in RLIP, p53, and PKC alpha represent essentially the entire spectrum of all human neoplasms. Elevated PKCa expression, failure of the cell cycle checkpoint (p53 dysfunction), and abnormal glutathione (GSH) metabolism are fundamental hallmarks of carcinogenesis and drug/radiation resistance. However, a lack of investigations into the interactions between these important regulatory nodes has fundamentally limited our understanding of carcinogenesis and the development of effective interventions for cancer prevention and therapy. Loss of p53, perhaps the most powerful tumor suppressor gene, predisposes rodents to spontaneous cancer and humans to familial, as well as acquired, cancers. Until recently, no genetic manipulation of any oncogene had been reported to abrogate spontaneous carcinogenesis in p53(-/-) rodent models. However, the overexpression of RLIP, a GSH-electrophile conjugate (GS-E) transporter, has been found to enhance cancer cell proliferation and confer drug/radiation resistance, whereas its depletion causes tumor regression, suggesting its importance in cancer and drug/radiation resistance. Indeed, RLIP is an essential effector of p53 that is necessary for broad cancer-promoting epigenetic remodeling. Interestingly, through a haploinsufficiency mechanism, the partial depletion of RLIP in p53(-/-) mice provides complete protection from neoplasia. Furthermore, RLIP / mice exhibit altered p53(-/-) and PKC alpha function, marked deficiency in clathrin-dependent endocytosis (CDE), and almost total resistance to chemical carcinogenesis. Based on these findings, in this review, we present a novel and radical hypothesis that expands our understanding of the highly significant cross-talk between p53, PKC alpha, and GSH signaling by RLIP in multiple tumor models.
Keyword:
RLIP
RalBP1
p53
PKC alpha
Drug resistance
Metastasis
Glutathione-electrophile conjugate
Mercapturic acid pathway
Therapeutics
AI总结
对已上传原文的论文进行重点信息的提取，主要内容包括：简要概述、研究摘要、背景介绍、关键亮点、图文解析、展望与总结。
期刊
B
IF:
8.3
论文数:
2.0K
被引数:
1.1W
机构
引用论文
Tapping the therapeutic potential of protein tyrosine phosphatase 4A with small molecule inhibitorsOAAI
OAAI分享收藏
Increased expression of cdc2 inhibits transport function of RLIP76 and promotes apoptosis.png)
CANCER LETTERSOAAI
CANCER LETTERSIF10.1
OAAI分享收藏
查看更多内容