Weber Janine, Polo Simona, Maspero Elena
Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.
Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, Milan, Italy.
Front Physiol. 2019 Apr 3;10:370. doi: 10.3389/fphys.2019.00370. eCollection 2019.
Ubiquitination plays a pivotal role in several cellular processes and is critical for protein degradation and signaling. E3 ubiquitin ligases are the matchmakers in the ubiquitination cascade, responsible for substrate recognition. In order to achieve selectivity and specificity on their substrates, HECT E3 enzymes are tightly regulated and exert their function in a spatially and temporally controlled fashion in the cells. These characteristics made HECT E3s intriguing targets in drug discovery in the context of cancer biology.
泛素化在多个细胞过程中发挥着关键作用,对蛋白质降解和信号传导至关重要。E3泛素连接酶是泛素化级联反应中的“媒人”,负责底物识别。为了实现对其底物的选择性和特异性,HECT E3酶受到严格调控,并在细胞中以空间和时间控制的方式发挥其功能。在癌症生物学背景下,这些特性使HECT E3酶成为药物研发中引人关注的靶点。