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 participa...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.展开更多
基金Swedish Research Council 2013- 3074 (Vetenskapsradet) and Erik och Edith Fernstroms foundation 2012 to S.G., G.H., and A.V.N., COST Proteostasis (BM1307- 040917-087135) to S.G. and A.V.N., Taishan Scholar's program to G.T., the National Natural Science Foundation of China (31671139 to M.J. and 31771284 to G.T.)Natural Science Foundation of Shandong Province, China (ZR2016)L026) to G.T., and the Key Research and Development Plan of Shandong Province (2017GSF18103) to MJ. G.H. is partially supported by KID Karolinska Institutet (C333802033)+2 种基金Also financial support from Ake Wiberg Foundation (Ml4-0127)Magnus Bergvall Foundation (2015-01200, 2016-01675)Carl Trygger Foun dation (CST 15:57) to S.B.L. are ack no wledged.
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.
