# 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.

## Key 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.