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

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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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Lee, C. S., Yi, J. S., Jung, S. Y., Kim, B. W., Lee, N. R., Choo, H. J., Jang, S. Y., Han, J., Chi, S. G., Park, M., Lee, J. H., & Ko, Y. G. (2010). TRIM72 negatively regulates myogenesis via targeting insulin receptor substrate-1. Cell Death and Differentiation, 17(8), 1254-1265. https://doi.org/10.1038/cdd.2010.1