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Current Protein & Peptide Science

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ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

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Review Article

Dynamics of Ubiquitination in Differentiation and Dedifferentiation of Pancreatic β-cells: Putative Target for Diabetes

Author(s): Meenal Francis, Smitha Bhaskar, Sreya Vishnuvajhala, Jyothi Prasanna and Anujith Kumar*

Volume 23, Issue 9, 2022

Published on: 12 October, 2022

Page: [602 - 618] Pages: 17

DOI: 10.2174/1389203723666220422092023

Price: $65

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Abstract

Impairment in the function of insulin-producing pancreatic β-cells is a hallmark of both type 1 and 2 diabetes (T1D/T2D). Despite over a century of effort, there is still no precise treatment regimen available for acute diabetes. Enhancing the endogenous β-cells either by protecting them from apoptosis or dedifferentiation is a classic alternative to retaining the β-cell pool. Recent reports have acknowledged the protein homeostasis mediated by the ubiquitin-proteasome system as one of the essential components in maintaining the β-cell pool. Degradation of the targeted substrate by the proteasome is majorly regulated by the ubiquitination status of the targeted protein dictated by E3 ligases and deubiquitinase enzymes. Imbalance in the function of these enzymes results in the malfunction of β-cells and, subsequently, hyperglycemia. Ubiquitination involves the covalent attachment of one or more ubiquitin moieties to the target protein by E3 ubiquitin ligases and deubiquitinases (DUBs) are the enzymes that antagonize the action of E3 ligases. Knowing different E3 ligases and deubiquitinases in the process of differentiation and dedifferentiation of β-cells probably paves the way for designing novel modulators that enhance either the differentiation or abate the dedifferentiation process. In this review, we will discuss the importance of the balanced ubiquitination process, an understanding of which would facilitate the restraining of β-cells from exhaustion.

Keywords: Diabetes, intracellular protein degradation, proteasome, pancreas, dedifferentiation, differentiation.

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