From seeds to trees: how E2 enzymes grow ubiquitin chains

Abstract

Modification of proteins by ubiquitin is a highly regulated process that plays a critical role in eukaryotes, from the construction of signalling platforms to the control of cell division. Aberrations in ubiquitin transfer are associated with many diseases, including cancer and neurodegenerative disorders. The ubiquitin machinery generates a rich code on substrate proteins, spanning from single ubiquitin modifications to polyubiquitin chains with diverse linkage types. Central to this process are the E2 enzymes, which often determine the exact nature of the ubiquitin code. The focus of this mini-review is on the molecular details of how E2 enzymes can initiate and grow ubiquitin chains. In particular, recent developments and biochemical breakthroughs that help explain how the degradative E2 enzymes, Ube2s, Ube2k, and Ube2r, generate complex ubiquitin chains with exquisite specificity will be discussed.

Prognostic and Immune Landscape Analysis of Ubiquitination-related Genes in Hepatocellular Carcinoma: Based on Bulk and Single-cell RNA Sequencing Data

“…CDC20 has emerged as a promising therapeutic target for cancer treatment, as reported by researchers 35 . UBE2S, a ubiquitin-conjugating enzyme, regulates cell cycle progression, apoptosis, and protein ubiquitination, which are directly associated with tumor growth 36 . UBE2S serves as a predictive biomarker for patients, and the UBE2S-PTEN-pAKT signaling axis holds promise as a therapeutic target for HCC 37 .…”