title: MG53-induced IRS-1 ubiquitination negatively regulates skeletal myogenesis and insulin signalling.
abstract: 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.
authors: Department of Life Sciences, Korea University, Seoul 136-701, Korea.
authors: Jae-Sung
authors: JS
authors: Yi
authors: Jun Sub
authors: JS
authors: Park
authors: Young-Mi
authors: YM
authors: Ham
authors: Nga
authors: N
authors: Nguyen
authors: Na-Rae
authors: NR
authors: Lee
authors: Jin
authors: J
authors: Hong
authors: Bong-Woo
authors: BW
authors: Kim
authors: Hyun
authors: H
authors: Lee
authors: Chang-Seok
authors: CS
authors: Lee
authors: Byung-Cheon
authors: BC
authors: Jeong
authors: Hyun Kyu
authors: HK
authors: Song
authors: Hana
authors: H
authors: Cho
authors: Yoon Ki
authors: YK
authors: Kim
authors: Jae-Seon
authors: JS
authors: Lee
authors: Kyong Soo
authors: KS
authors: Park
authors: Haksub
authors: H
authors: Shin
authors: Inho
authors: I
authors: Choi
authors: Seung Hee
authors: SH
authors: Lee
authors: Woo Jin
authors: WJ
authors: Park
authors: Shi-Young
authors: SY
authors: Park
authors: Cheol Soo
authors: CS
authors: Choi
authors: Peihui
authors: P
authors: Lin
authors: Malith
authors: M
authors: Karunasiri
authors: Tao
authors: T
authors: Tan
authors: Pu
authors: P
authors: Duann
authors: Hua
authors: H
authors: Zhu
authors: Jianjie
authors: J
authors: Ma
authors: Young-Gyu
authors: YG
authors: Ko
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D003920:Diabetes Mellitus / Q000378:metabolism; D059305:Diet, High-Fat; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D002352:Carrier Proteins; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; C538824:MG53 protein, mouse; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D044763:Ubiquitin-Conjugating Enzymes
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