The Ubiquitin Proteasome System and Skin Fibrosis

Overview

Journal Mol Diagn Ther

Specialties Molecular Biology
Pathology
Pharmacology

Date 2021 Jan 12

PMID 33433895

Citations 11

Authors

Wanlu Shen

Zhigang Zhang

Jiaqing Ma

Di Lu

Lechun Lyu

Affiliations

Soon will be listed here.

Abstract

The ubiquitin proteasome system (UPS) is a highly conserved way to regulate protein turnover in cells. The UPS hydrolyzes and destroys variant or misfolded proteins and finely regulates proteins involved in differentiation, apoptosis, and other biological processes. This system is a key regulatory factor in the proliferation, differentiation, and collagen secretion of skin fibroblasts. E3 ubiquitin protein ligases Parkin and NEDD4 regulate multiple signaling pathways in keloid. Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) binding with deubiquitinase USP10 can induce p53 destabilization and promote keloid-derived fibroblast proliferation. The UPS participates in the occurrence and development of hypertrophic scars by regulating the transforming growth factor (TGF)-β/Smad signaling pathway. An initial study suggests that TNFα-induced protein 3 (TNFAIP3) polymorphisms may be significantly associated with scleroderma susceptibility in individuals of Caucasian descent. Sumoylation and multiple ubiquitin ligases, including Smurfs, UFD2, and KLHL42, play vital roles in scleroderma by targeting the TGF-β/Smad signaling pathway. In the future, drugs targeting E3 ligases and deubiquitinating enzymes have great potential for the treatment of skin fibrosis.

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