作者
Adam R Blanden, Xin Yu, Stewart N Loh, Arnold J Levine, Darren R Carpizo
发表日期
2015/11/1
来源
Drug discovery today
卷号
20
期号
11
页码范围
1391-1397
出版商
Elsevier Current Trends
简介
Highlights
- Reactivating mutant p53 through zinc metallochaperones.
- Zinc metallochaperones restore zinc to zinc-deficient mutant p53.
- Zinc metallochaperones function by ionophore and buffer activity.
- Zinc metallochaperones rely on ROS to transactivate mutant p53.
Tumor protein p53 (TP53) is the most commonly mutated gene in human cancer. The majority of mutations are missense, and generate a defective protein that is druggable. Yet, for decades, the small-molecule restoration of wild-type (WT) p53 function in mutant p53 tumors (so-called p53 mutant ‘reactivation’) has been elusive to researchers. The p53 protein requires the binding of a single zinc ion for proper folding, and impairing zinc binding is a major mechanism for loss of function in missense mutant p53. Here, we describe recent work defining a new class of drugs termed zinc metallochaperones that restore WT p53 structure and function by restoring …
学术搜索中的文章
AR Blanden, X Yu, SN Loh, AJ Levine, DR Carpizo - Drug discovery today, 2015