Abstract
The widely studied p53 protein is a target of many anti-cancer drugs because it is often inactivated either by point mutations or by allelic deletion in many cancers. The expression of p53 is tightly controlled primarily by MDM2, its prototypical negative regulator, and by a number of other negative regulators including E3 ubiquitin ligases and acetyltransferases. Notably, the activity of MDM2 can be enhanced by the retinoblastoma binding protein 6 (RBBP6), which possesses E3 ubiquitin ligase activity and p53-binding capabilities. One of the strategies employed for designing anti-cancer drugs based on the p53 pathway is to activate p53 directly or to target its negative regulators. A small number of drugs, aimed at the regulatory molecules, is emerging. In this chapter, drugs targeting p53 and the regulatory elements in the pathway are scrutinized and the potential for RBBP6 as a drug target is also considered.
Keywords: Anti-cancer drugs, E3 ubiquitin ligases, MDM2, p53, RBBP6.
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