title: Ret finger protein mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy.
abstract: Skeletal muscle atrophy results from the net loss of muscular proteins and organelles and is caused by pathologic conditions such as nerve injury, immobilization, cancer, and other metabolic diseases. Recently, ubiquitination-mediated degradation of skeletal-muscle-specific transcription factors was shown to be involved in muscle atrophy, although the mechanisms have yet to be defined. Here we report that ret finger protein (RFP), also known as TRIM27, works as an E3 ligase in Pax7-induced degradation of MyoD. Muscle injury induced by sciatic nerve transection up-regulated RFP and RFP physically interacted with both Pax7 and MyoD. RFP and Pax7 synergistically reduced the protein amounts of MyoD but not the mRNA. RFP-induced reduction of MyoD protein was blocked by proteasome inhibitors. The Pax7-induced reduction MyoD was attenuated by RFP siRNA and by MG132, a proteasome inhibitor. RFPΔR, an RFP construct that lacks the RING domain, failed to reduce MyoD amounts. RFP ubiquitinated MyoD, but RFPΔR failed to do so. Forced expression of RFP, but not RFPΔR, enhanced Pax7-induced ubiquitination of MyoD, whereas RFP siRNA blocked the ubiquitination. Sciatic nerve injury-induced muscle atrophy as well the reduction in MyoD was attenuated in RFP knockout mice. Taken together, our results show that RFP works as a novel E3 ligase in the Pax7-mediated degradation of MyoD in response to skeletal muscle atrophy.
authors.affiliation: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea; BK21 Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Hosouk
authors.initials: H
authors.lastname: Joung
authors.affiliation: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea; Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea; BK21 Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Gwang Hyeon
authors.initials: GH
authors.lastname: Eom
authors.affiliation: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Nakwon
authors.initials: N
authors.lastname: Choe
authors.affiliation: Department of Anatomy, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Hye Mi
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Jeong-Hyeon
authors.initials: JH
authors.lastname: Ko
authors.affiliation: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea; BK21 Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Duk-Hwa
authors.initials: DH
authors.lastname: Kwon
authors.affiliation: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea; BK21 Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Yoon Seok
authors.initials: YS
authors.lastname: Nam
authors.affiliation: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea; BK21 Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Hyunki
authors.initials: H
authors.lastname: Min
authors.affiliation: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Sera
authors.initials: S
authors.lastname: Shin
authors.affiliation: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea; BK21 Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Jeewon
authors.initials: J
authors.lastname: Kook
authors.affiliation: Department of Pediatrics, Chonnam National University Hospital, Gwangju 501-746, Republic of Korea.
authors.forename: Young Kuk
authors.initials: YK
authors.lastname: Cho
authors.affiliation: Department of Surgery, Chonnam National University Hospital, Gwangju 501-746, Republic of Korea.
authors.forename: Jeong Chul
authors.initials: JC
authors.lastname: Kim
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea.
authors.forename: Sang Beom
authors.initials: SB
authors.lastname: Seo
authors.affiliation: Department of Pharmacology, College of Medicine, Seonam University, Namwon, Republic of Korea.
authors.forename: Yung Hong
authors.initials: YH
authors.lastname: Baik
authors.affiliation: Department of Anatomy, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea; BK21 Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Kwang-Il
authors.initials: KI
authors.lastname: Nam
authors.affiliation: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea; Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea; BK21 Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea. Electronic address: kookhyun@chonnam.ac.kr.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kook
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology*; D017570:MyoD Protein / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051763:PAX7 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D011485:Protein Binding; D059748:Proteolysis / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012038:Regeneration; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination / Q000187:drug effects; D000070584:Tripartite Motif Proteins
chemical_list: D004268:DNA-Binding Proteins; D007976:Leupeptins; D017570:MyoD Protein; D009687:Nuclear Proteins; D051763:PAX7 Transcription Factor; D011480:Protease Inhibitors; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases; C497322:Pax7 protein, mouse; C489296:Trim27 protein, mouse; D000070584:Tripartite Motif Proteins; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: MyoD; Pax7; Ret finger protein; Skeletal muscle atrophy; Ubiquitination