Cancer Drugs Targeting the p53 Regulatory Machinery
Pp. 199-230 (32)
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.
Anti-cancer drugs, E3 ubiquitin ligases, MDM2, p53, RBBP6.
School of Molecular and Cell Biology, Gatehouse 512, University of the Witwatersrand, Johannesburg, South Africa.