TRIM72 negatively regulates myogenesis via targeting insulin receptor substrate-1
TRIM72 negatively regulates myogenesis via targeting insulin receptor substrate-1
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DOI：
10.1038/cdd.2010.1
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发表时间：
2010-08-01
影响因子：
12.4
通讯作者：
Ko, Y-G
中科院分区：
文献类型：
--
作者：
Lee, C. S.;Yi, J-S;Ko, Y-G
脂筏是启动胰岛素样生长因子（IGF）诱导骨骼肌分化和肥大的细胞信号转导的平台。在这里，三重基序72（TRIM 72），一个真正有趣的新基因（RING）指结构域，一个B盒，两个卷曲螺旋结构域，和SPRY（SPla和RYanodine受体）结构域，被发现主要表达在骨骼肌和心肌的肌膜脂筏。腺病毒TRIM 72过表达通过TRIM 72与IRS-1的分子结合调节IGF诱导的胰岛素受体底物-1（IRS-1）活化，阻止了C2 C12肌生成，但RNAi介导的TRIM 72沉默增强了C2 C12肌生成。此外，与TRIM 72（+/+）小鼠相比，TRIM 72（-/-）小鼠卫星细胞中IGF诱导的Akt活化增加，肌生成活性高度增强。由于TRIM 72启动子分析表明，TRIM 72启动子的两个近端E-box是MyoD和Akt依赖的TRIM 72转录所必需的，因此我们可以得出结论，TRIM 72是IRS-1的新拮抗剂，并且是IGF诱导的肌肉分化的负调节剂。Cell Death and Differentiation（2010）17，1254-1265; doi：10.1038/cdd.2010.1; 2010年2月5日在线发表
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. Cell Death and Differentiation (2010) 17, 1254-1265; doi:10.1038/cdd.2010.1; published online 5 February 2010