MG53-induced IRS-1 ubiquitination negatively regulates skeletal myogenesis and insulin signalling
- Authors
- Yi, Jae-Sung; Park, Jun Sub; Ham, Young-Mi; Nguyen, Nga; Lee, Na-Rae; Hong, Jin; Kim, Bong-Woo; Lee, Hyun; Lee, Chang-Seok; Jeong, Byung-Cheon; Song, Hyun Kyu; Cho, Hana; Kim, Yoon Ki; Lee, Jae-Seon; Park, Kyong Soo; Shin, Haksub; Choi, Inho; Lee, Seung Hee; Park, Woo Jin; Park, Shi-Young; Choi, Cheol Soo; Lin, Peihui; Karunasiri, Malith; Tan, Tao; Duann, Pu; Zhu, Hua; Ma, Jianjie; Ko, Young-Gyu
- Issue Date
- 8월-2013
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- MG53; IRS-1; ubiquitination; insulin signalling; insulin resistance; myogenesis
- Citation
- NATURE COMMUNICATIONS, v.4
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE COMMUNICATIONS
- Volume
- 4
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/102632
- DOI
- 10.1038/ncomms3354
- ISSN
- 2041-1723
- 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.