Progress in Anticancer Drug Development Targeting Ubiquitination-Related Factors

Abstract

Ubiquitination is extensively involved in critical signaling pathways through monitoring protein stability, subcellular localization, and activity. Dysregulation of this process results in severe diseases including malignant cancers. To develop drugs targeting ubiquitination-related factors is a hotspot in research to realize better therapy of human diseases. Ubiquitination comprises three successive reactions mediated by Ub-activating enzyme E1, Ub-conjugating enzyme E2, and Ub ligase E3. As expected, multiple ubiquitination enzymes have been highlighted as targets for anticancer drug development due to their dominant effect on tumorigenesis and cancer progression. In this review, we discuss recent progresses in anticancer drug development targeting enzymatic machinery components.

SKP2‐mediated ubiquitination and degradation of KLF11 promotes osteoarthritis via modulation of JMJD3/NOTCH1 pathway

“…Ubiquitination can be modulated by various enzymes including activating E1, conjugating E2, and ligase E3 enzymes. S‐phase kinase‐associated protein 2 (SKP2) is an important E3 ligase that recognizes target proteins to facilitate their ubiquitination 9 . SKP2 was found to be highly expressed in patients with OA 10 .…”

“…S-phase kinaseassociated protein 2 (SKP2) is an important E3 ligase that recognizes target proteins to facilitate their ubiquitination. 9 SKP2 was found to be highly expressed in patients with OA. 10 Jian et al found that miR-337-3p attenuated IL-1β-induced synovial fibroblast damage via SKP2-mediated ubiquitination and degradation of dual-specificity protein phosphatase1.…”