| 1 | Muscle RING-finger protein-1 (MuRFl) functions and cellular localization are regulated by SUMOl post-translational modification显示文摘The muscle RING-finger protein-1 (MuRFl) is an E3 ubiquitin ligase expressed in skeletal and cardiac muscle tissues and it plays important roles in muscle remodeling. Upregulation of MuRFl gene transcription participates in skeletal muscle atrophy, on contrary downregulation of protein expression leads to cardiac hypertrophy. MuRFl gene point mutations have been found to generate protein aggregate myopathies defined as muscle disorder characterized by protein accumulation in muscle fibers. We have discovered that MuRFl turned out to be also a target for a new post-translational modification arbitrated by conjugation of SUM01 and it is mediated by the SUMO ligases E2 UBC9 and the E3 PIASy/4. SUMOylation takes place at lysine 238 localized at the second coiled-coil protein domain that is required for efficient substrate interaction for polyubiquitination. We provided evidence that SUMOylation is essential for MuRFl nuclear translocation and its mitochondria accumulation is enhanced in hyper? glycemic conditions delivering a stabilization of the overall SUMOylated proteins in cultured myocytes. Thus, our findings add this SUM01 post-translational modification as a new concept to understand muscle disorders related to the defect in MuRFl activity. | Gabriel Heras Arvind Venkat Namuduri Leonardo Traini Ganna Shevchenko Alexander Falk Sara Bergstrom Lind Mi Jia Geng Tian Stefano Gastaldello | 2019 | Journal of Molecular Cell Biology2019，11，5： | 4 |
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