Regulation of biological processes by ubiquitin ligases: a focus on the Pagano Lab’s contribution

TL;DR

This paper discusses how ubiquitin ligases regulate protein degradation and other cellular functions, highlighting the Pagano Lab's contributions.

Contribution

The paper emphasizes the Pagano Lab's role in advancing understanding of ubiquitin ligases' diverse functions beyond protein degradation.

Findings

Ubiquitin ligases are involved in various post-translational modifications that regulate protein degradation.

Different types of ubiquitylation signals control cellular functions like signal transduction and protein localization.

Abstract

Protein homeostasis depends on many fundamental processes including mRNA synthesis, translation, post-translational modifications, and proteolysis. In the late 70s and early 80s the discovery that the small 76 amino acid protein ubiquitin could be attached to target proteins via a multi-stage process involving ubiquitin-activating enzymes, ubiquitin conjugating enzymes, and ubiquitin ligases, revealed an exciting new post-translational mechanism to regulate protein degradation. This cellular system was uncovered using biochemical methods by Avram Hershko, who would later won the Nobel prize for this discovery; however, the biological functions of ubiquitin ligases remained unknown for many years. It was initially described that ubiquitin modifies proteins at one or more lysine residues and once a long ubiquitin chain was assembled, proteins were degraded by the proteasome. Now we know that proteins can be mono-, multimono-, homotypic poly-, or heterotypic poly-ubiquitylated, each of which confers a specific signal that goes beyond protein degradation regulating additional key cellular functions such as signal transduction, protein localization, recognition of damaged proteins, etc.

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