Role of the tripartite motif-containing (TRIM) family of proteins in insulin resistance and related disorders

Diabetes Obes Metab. 2024 Jan;26(1):3-15. doi: 10.1111/dom.15294. Epub 2023 Sep 19.

Abstract

Emerging evidence suggests that the ubiquitin-mediated degradation of insulin-signalling-related proteins may be involved in the development of insulin resistance and its related disorders. Tripartite motif-containing (TRIM) proteins, a superfamily belonging to the E3 ubiquitin ligases, are capable of controlling protein levels and function by ubiquitination, which is essential for the modulation of insulin sensitivity. Recent research has indicated that some of these TRIMs act as key regulatory factors of metabolic disorders such as type 2 diabetes mellitus, obesity, nonalcoholic fatty liver disease, and atherosclerosis. This review provides a comprehensive overview of the latest evidence linking TRIMs to the regulation of insulin resistance and its related disorders, their roles in regulating multiple signalling pathways or cellular processes, such as insulin signalling pathways, peroxisome proliferator-activated receptor signalling pathways, glucose and lipid metabolism, the inflammatory response, and cell cycle control, as well as recent advances in the development of TRIM-targeted drugs.

Keywords: E3 ubiquitin ligase; asthma; cardiac inflammation; inflammation; metabolic disorders; ubiquitination.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2*
  • Humans
  • Insulin Resistance*
  • Insulins*
  • Tripartite Motif Proteins / genetics
  • Tripartite Motif Proteins / metabolism
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • Ubiquitin-Protein Ligases
  • Ubiquitin
  • Tripartite Motif Proteins
  • Insulins