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 language | English |
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Pages (from-to) | 1254-1265 |
Number of pages | 12 |
Journal | Cell Death and Differentiation |
Volume | 17 |
Issue number | 8 |
DOIs | |
Publication status | Published - 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