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Molecular Mechanisms of DUBs Regulation in Signaling and Disease. | LitMetric

Molecular Mechanisms of DUBs Regulation in Signaling and Disease.

Int J Mol Sci

Departament de Bioquimica i Biologia Molecular, Institut de Biotecnologia i de Biomedicina, Universitat Autonòma de Barcelona, 08193 Bellaterra, Spain.

Published: January 2021

AI Article Synopsis

  • Deubiquitinating enzymes (DUBs) play a vital role in regulating processes within cells by managing protein ubiquitination, which is essential for maintaining protein balance through the ubiquitin-proteasome system.
  • This review highlights recent discoveries about the molecular mechanisms and specificities of different DUBs, emphasizing structural biology's role in understanding how these enzymes operate at a detailed level.
  • The discussion also covers strategies for DUBs to selectively cleave specific ubiquitin linkages and explores the progress in developing drugs targeting DUB proteases, which are linked to diseases like cancer and neurodegenerative disorders.

Article Abstract

The large family of deubiquitinating enzymes (DUBs) are involved in the regulation of a plethora of processes carried out inside the cell by protein ubiquitination. Ubiquitination is a basic pathway responsible for the correct protein homeostasis in the cell, which could regulate the fate of proteins through the ubiquitin-proteasome system (UPS). In this review we will focus on recent advances on the molecular mechanisms and specificities found for some types of DUBs enzymes, highlighting illustrative examples in which the regulatory mechanism for DUBs has been understood in depth at the molecular level by structural biology. DUB proteases are responsible for cleavage and regulation of the multiple types of ubiquitin linkages that can be synthesized inside the cell, known as the ubiquitin-code, which are tightly connected to specific substrate functions. We will display some strategies carried out by members of different DUB families to provide specificity on the cleavage of particular ubiquitin linkages. Finally, we will also discuss recent progress made for the development of drug compounds targeting DUB proteases, which are usually correlated to the progress of many pathologies such as cancer and neurodegenerative diseases.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863924PMC
http://dx.doi.org/10.3390/ijms22030986DOI Listing

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