Tripartite Motif-Containing Protein 32 (TRIM32): What Does It Do for Skeletal Muscle?

Cells. 2023 Aug 19;12(16):2104. doi: 10.3390/cells12162104.

Abstract

Tripartite motif-containing protein 32 (TRIM32) is a member of the tripartite motif family and is highly conserved from flies to humans. Via its E3 ubiquitin ligase activity, TRIM32 mediates and regulates many physiological and pathophysiological processes, such as growth, differentiation, muscle regeneration, immunity, and carcinogenesis. TRIM32 plays multifunctional roles in the maintenance of skeletal muscle. Genetic variations in the TRIM32 gene are associated with skeletal muscular dystrophies in humans, including limb-girdle muscular dystrophy type 2H (LGMD2H). LGMD2H-causing genetic variations of TRIM32 occur most frequently in the C-terminal NHL (ncl-1, HT2A, and lin-41) repeats of TRIM32. LGMD2H is characterized by skeletal muscle dystrophy, myopathy, and atrophy. Surprisingly, most patients with LGMD2H show minimal or no dysfunction in other tissues or organs, despite the broad expression of TRIM32 in various tissues. This suggests more prominent roles for TRIM32 in skeletal muscle than in other tissues or organs. This review is focused on understanding the physiological roles of TRIM32 in skeletal muscle, the pathophysiological mechanisms mediated by TRIM32 genetic variants in LGMD2H patients, and the correlations between TRIM32 and Duchenne muscular dystrophy (DMD).

Keywords: DMD; LGMD2H; NHL repeats; TRIM32; muscular dystrophy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atrophy
  • Humans
  • Muscle, Skeletal
  • Muscular Dystrophies, Limb-Girdle* / genetics
  • Muscular Dystrophy, Duchenne*
  • Transcription Factors
  • Tripartite Motif Proteins / genetics
  • Ubiquitin-Protein Ligases / genetics

Substances

  • TRIM32 protein, human
  • Tripartite Motif Proteins
  • Transcription Factors
  • Ubiquitin-Protein Ligases

Supplementary concepts

  • Limb-girdle muscular dystrophy type 2H

Grants and funding

This work was supported by the Mid-career Researcher Program through National Research Foundation of Korea grants (No. NRF-2022R1A2C1005362 to E.H.L.).