MG53-induced IRS-1 ubiquitination negatively regulates skeletal myogenesis and insulin signalling
Mitsugumin 53 (MG53) negatively regulates skeletal myogenesis by targeting insulin receptor substrate 1 (IRS-1). Here, we show that MG53 is an ubiquitin E3 ligase that induces IRS-1 ubiquitination with the help of an E2-conjugating enzyme, UBE2H. Molecular manipulations that disrupt the E3-ligase...
Đã lưu trong:
| Príomhúdar: | |
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| Formáid: | Journal article |
| Teanga: | English |
| Foilsithe: |
Springer
2022
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| Ábhair: | |
| Rochtain Ar Líne: | http://scholar.dlu.edu.vn/handle/123456789/1569 |
| Clibeanna: |
Cuir Clib Leis
Gan Chlibeanna, Bí ar an gcéad duine leis an taifead seo a chlibeáil!
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| Thư viện lưu trữ: | Thư viện Trường Đại học Đà Lạt |
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| Achoimre: | Mitsugumin 53 (MG53) negatively regulates skeletal myogenesis by targeting insulin receptor
substrate 1 (IRS-1). Here, we show that MG53 is an ubiquitin E3 ligase that induces IRS-1
ubiquitination with the help of an E2-conjugating enzyme, UBE2H. Molecular manipulations
that disrupt the E3-ligase function of MG53 abolish IRS-1 ubiquitination and enhance
skeletal myogenesis. Skeletal muscles derived from the MG53 / mice show an elevated
IRS-1 level with enhanced insulin signalling, which protects the MG53 / mice from
developing insulin resistance when challenged with a high-fat/high-sucrose diet. Muscle
samples derived from human diabetic patients and mice with insulin resistance show normal
expression of MG53, indicating that altered MG53 expression does not serve as a causative
factor for the development of metabolic disorders. Thus, therapeutic interventions that target
the interaction between MG53 and IRS-1 may be a novel approach for the treatment of
metabolic diseases that are associated with insulin resistance. |
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