TRIM72 negatively regulates myogenesis via targeting insulin receptor substrate-1

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 À/À mice, compared to those of TRIM72 þ / þ 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.

The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation

“…Recently, Trim72 has been shown to ubiquitinate IRS-1 and the insulin receptor (99,123). Knockout of Trim72 in mice leads to increased Akt activation and increased myogenesis (55,123). Another ligase, Trim32, negatively regulates Akt signaling by causing the dissociation between plakoglobin and phosphatidylinositol 3-kinase (14).…”

Mitochondrial Complex I Deficiency Enhances Skeletal Myogenesis but Impairs Insulin Signaling through SIRT1 Inactivation

“…The mitsugumin 53 (MG53) promoter-luciferase reporter gene was previously generated (40). Gene transfection was performed using electroporation according to the protocol of electroporator MP-100 (Invitrogen) for C2C12 myoblasts.…”

Mitsugumin 53 (MG53) Ligase Ubiquitinates Focal Adhesion Kinase during Skeletal Myogenesis

“…It has been proposed that mitsugumin 53 (MG53), also known as tripartite motif-containing 72 (TRIM72), is a novel E3 ligase that induces ubiquitination and proteasomal degradation of insulin receptor substrate 1 (IRS-1) in skeletal muscle (12)(13)(14). MG53 is highly up-regulated during skeletal myogenesis because its promoter contains E-box-and myocyte enhancer factor-binding sites, which are binding sites for MyoD and myocyte enhancer factor, respectively (15).…”