The roles of ubiquitination in extrinsic cell death pathways and its implications for therapeutics.

The roles of ubiquitination in extrinsic cell death pathways and its implications for therapeutics. Biochem Pharmacol. 2018 Nov 16;: Authors: Seo J, Wook Kim M, Bae KH, Lee SC, Song J, Lee EW Abstract Regulation of cell survival and death, including apoptosis and necroptosis, is important for normal development and tissue homeostasis, and disruption of these processes can cause cancer, inflammatory diseases, and degenerative diseases. Ubiquitination is a cellular process that induces proteasomal degradation by covalently attaching ubiquitin to the substrate protein. In addition to proteolytic ubiquitination, nonproteolytic ubiquitination, such as M1-linked and K63-linked ubiquitination, has been shown to be important in recent studies, which have demonstrated its function in cell signaling pathways that regulate inflammation and cell death pathways. In this review, we summarize the TRAIL- and TNF-induced death receptor signaling pathways along with recent advances in this field and illustrate how different types of ubiquitination control cell death and survival. In particular, we provide an overview of the different types of ubiquitination, target residues, and modifying enzymes, including E3 ligases and deubiquitinating enzymes. Given the relevance of these regulatory pathways in human disease, we hope that a better understanding of the regulatory mechanisms of cell death pathways will provide insights into and therapeutic strategie...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research