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MG53-induced IRS-1 ubiquitination negatively regulates skeletal myogenesis and insulin signalling

Author

Listed:
  • Jae-Sung Yi

    (Korea University)

  • Jun Sub Park

    (Korea University)

  • Young-Mi Ham

    (Korea University)

  • Nga Nguyen

    (Korea University)

  • Na-Rae Lee

    (Korea University)

  • Jin Hong

    (Korea University)

  • Bong-Woo Kim

    (Korea University)

  • Hyun Lee

    (Korea University)

  • Chang-Seok Lee

    (Korea University)

  • Byung-Cheon Jeong

    (Korea University)

  • Hyun Kyu Song

    (Korea University)

  • Hana Cho

    (Korea University)

  • Yoon Ki Kim

    (Korea University)

  • Jae-Seon Lee

    (Korea Institute of Radiological and Medical Sciences)

  • Kyong Soo Park

    (Seoul National University College of Medicine)

  • Haksub Shin

    (Yonsei University, Gangwon-Do)

  • Inho Choi

    (Yonsei University, Gangwon-Do)

  • Seung Hee Lee

    (College of Life Sciences, Gwangju Institute of Science and Technology)

  • Woo Jin Park

    (College of Life Sciences, Gwangju Institute of Science and Technology)

  • Shi-Young Park

    (Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute)

  • Cheol Soo Choi

    (Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute
    Gil Medical Center, Gachon University)

  • Peihui Lin

    (Davis Heart and Lung Research Institute, The Ohio State University)

  • Malith Karunasiri

    (Davis Heart and Lung Research Institute, The Ohio State University)

  • Tao Tan

    (Davis Heart and Lung Research Institute, The Ohio State University)

  • Pu Duann

    (Davis Heart and Lung Research Institute, The Ohio State University)

  • Hua Zhu

    (Davis Heart and Lung Research Institute, The Ohio State University)

  • Jianjie Ma

    (Davis Heart and Lung Research Institute, The Ohio State University)

  • Young-Gyu Ko

    (Korea University)

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.

Suggested Citation

  • Jae-Sung Yi & Jun Sub Park & Young-Mi Ham & Nga Nguyen & Na-Rae Lee & Jin Hong & Bong-Woo Kim & Hyun Lee & Chang-Seok Lee & Byung-Cheon Jeong & Hyun Kyu Song & Hana Cho & Yoon Ki Kim & Jae-Seon Lee & , 2013. "MG53-induced IRS-1 ubiquitination negatively regulates skeletal myogenesis and insulin signalling," Nature Communications, Nature, vol. 4(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3354
    DOI: 10.1038/ncomms3354
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    Cited by:

    1. Yuemin Ma & Lei Ding & Zhenhai Li & Chun Zhou, 2023. "Structural basis for TRIM72 oligomerization during membrane damage repair," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Myeong-Suk Bahn & Dong-Min Yu & Myoungwoo Lee & Sung-Je Jo & Ji-Won Lee & Ho-Chul Kim & Hyun Lee & Hong Lim Kim & Arum Kim & Jeong-Ho Hong & Jun Seok Kim & Seung-Hoi Koo & Jae-Seon Lee & Young-Gyu Ko, 2022. "Central role of Prominin-1 in lipid rafts during liver regeneration," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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