期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 287, 期 37, 页码 31330-31341出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.388785
关键词
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资金
- Japan Diabetes Foundation
- Hyogo Science and Technology Association
- Grants-in-Aid for Scientific Research [23790336, 23227005] Funding Source: KAKEN
Insulin-like growth factors (IGFs) are essential for the development, regeneration, and hypertrophy of skeletal muscles. IGF-II promotes myoblast differentiation through phosphatidylinositol 3-kinase (PI 3-kinase), Akt, and mTOR signaling. Here, we report that skeletal muscle-and kidney-enriched inositol polyphosphate phosphatase (SKIP) negatively regulates myogenesis through inhibition of IGF-II production and attenuation of the IGF-II-Akt-mTOR signaling pathway. We also demonstrate that SKIP expression, which was markedly elevated during differentiation, was controlled by MyoD in C2C12 cells. Expression of SKIP inhibited IGF-II at the transcription level. These results indicate that SKIP regulates MyoD-mediated muscle differentiation. Silencing of SKIP increased IGF-II transcription and myoblast differentiation. Furthermore, knockdown of SKIP resulted in thick myotubes with a larger number of nuclei than that in control C2C12 cells. Taken together, these data indicate that SKIP controls the IGF-II-PI 3-kinase-Akt-mTOR auto-regulation loop during myogenesis. Our findings identify SKIP as a key regulator of muscle cell differentiation.
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