TRIM72 negatively regulates myogenesis via targeting insulin receptor substrate-1

C. S. Lee, J. S. Yi, S. Y. Jung, B. W. Kim, N. R. Lee, H. J. Choo, S. Y. Jang, J. Han, S. G. Chi, M. Park, J. H. Lee, Y. G. Ko

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

Abstract

Lipid rafts have been known to be platforms to initiate cellular signal transduction of insulin-like growth factor (IGF) inducing skeletal muscle differentiation and hypertrophy. Here, tripartite motif 72 (TRIM72), with a really interesting new gene (RING)-finger domain, a B-box, two coiled-coil domains, and a SPRY (SPla and RYanodine receptor) domain, was revealed to be predominantly expressed in the sarcolemma lipid rafts of skeletal and cardiac muscles. Adenoviral TRIM72 overexpression prevented but RNAi-mediated TRIM72 silencing enhanced C2C12 myogenesis by modulating the IGF-induced insulin receptor substrate-1 (IRS-1) activation through the molecular association of TRIM72 with IRS-1. Furthermore, myogenic activity was highly enhanced with increased IGF-induced Akt activation in the satellite cells of TRIM72 mice, compared to those of TRIM72 mice. Because TRIM72 promoter analysis shows that two proximal E-boxes in TRIM72 promoter were essential for MyoD- and Akt-dependent TRIM72 transcription, we can conclude that TRIM72 is a novel antagonist of IRS-1, and is essential as a negative regulator of IGF-induced muscle differentiation.

Original languageEnglish
Pages (from-to)1254-1265
Number of pages12
JournalCell Death and Differentiation
Volume17
Issue number8
DOIs
Publication statusPublished - 2010 Aug

Bibliographical note

Funding Information:
Acknowledgements. We thank M-S Kim for CA-FOXO gene and E-J Choi for CA-GSK3b gene. We also thank Dr. Guy A Thompson for critical discussions. This work was supported by grants from the Center for New Drug Target Discovery of the Korea Ministry of Science and Technology (2006-02795), Korea Research Foundation (KRF-2005-C00358), and Korean Ministry of Public Health and Welfare (A090597) to Y-G Ko.

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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