The roles of ubiquitination‐mediated intrinsic apoptotic signalling in cancer therapy

Abstract

Ubiquitination, a highly versatile process of protein homeostasis, participates in the degradation of the vast majority of cellular proteins. In addition to proteolytic function, ubiquitination can also conduce to modulate cellular processes independent of proteolysis, such as signal transduction, protein trafficking, DNA repair and so on. Apoptosis modulates cell quantity via orderly removing damaged cells effectively and plays a fundamental role in the function of multicellular organisms as well homeostasis, while abnormal regulation of apoptosis can lead to various diseases, especially cancer. Since various tumour cells intrinsically elude apoptotic elimination, emerging strategies targeting induction of apoptosis have become great potential and often necessary cancer therapeutic approaches. Numerous researches have shown that ubiquitination can facilitate or inhibit apoptosis by utilising its proteolytic or non‐proteolytic functions aiming at controlling the levels of key proteins. In this review, we focused on intrinsic apoptosis and summarised how diverse types of ubiquitination regulate intrinsic apoptosis through E3 ligases and deubiquitinating enzymes. Given the mechanisms of ubiquitin‐mediated regulation of intrinsic apoptosis and their physiological relevance, we hope that it will supply more therapeutic strategies for cancer.