Skp2 Inhibitors: Novel Anticancer Strategies

Title:Skp2 Inhibitors: Novel Anticancer Strategies

Volume: 23 Issue: 22

Author(s): Yeongju Lee and Hyun-Suk Lim

Affiliation:

Keywords: 26S proteasome, E3 ligase complex, Skp2 inhibitors, Skp2/p27 interaction, Tumorigenesis, Ubiquitinproteasome system.

Abstract: Skp2 is frequently overexpressed in many human cancers and plays a key role in tumorigenesis. As a component of the SCF^Skp2 ubiquitin E3 ligase complex, Skp2 is responsible for recruiting substrate proteins for their ubiquitination and subsequent degradation by the 26S proteasome. Thus, Skp2 promotes the cell cycle by down-regulating cell cycle proteins such as the tumor suppressor p27. Alternatively, Skp2 suppresses p53-dependent apoptosis by outcompeting p53 for binding to p300, thereby perturbing p300-mediated p53 acetylation and stabilization. Taken together, inhibition of Skp2 functions (either proteolytic function or non-proteolytic function) is emerging as a promising and novel anti-cancer strategy. In the present review, we highlight the development of Skp2 inhibitors with different mechanisms of action.

Cite this article as:

Lee Yeongju and Lim Hyun-Suk, Skp2 Inhibitors: Novel Anticancer Strategies, Current Medicinal Chemistry 2016; 23 (22) . https://dx.doi.org/10.2174/0929867323666160510122624