title: Romo1 is a negative-feedback regulator of Myc.
abstract: Degradation of Myc protein is mediated by E3 ubiquitin ligases, including SCF(Fbw7) and SCF(Skp2), but much remains unknown about the mechanism of S-phase kinase-associated protein (Skp2)-mediated Myc degradation. In the present study, we show that upregulated Myc protein, which triggers the G1-S phase progression in response to growth-stimulatory signals, induces reactive oxygen species modulator 1 (Romo1) expression. Romo1 subsequently triggers Skp2-mediated ubiquitylation and degradation of Myc by a mechanism not previously reported in normal lung fibroblasts. We also show that reactive oxygen species (ROS) derived from steady-state Romo1 expression are necessary for cell cycle entry of quiescent cells. From this study, we suggest that the generation of ROS mediated by pre-existing Romo1 protein is required for Myc induction. Meanwhile, Romo1 expression induced by Myc during G1 phase stimulates Skp2-mediated Myc degradation in a negative-feedback mechanism.
authors.affiliation: Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705, Republic of Korea.
authors.forename: Seung Baek
authors.initials: SB
authors.lastname: Lee
authors.forename: Jung Jin
authors.initials: JJ
authors.lastname: Kim
authors.forename: Jin Sil
authors.initials: JS
authors.lastname: Chung
authors.forename: Myeong-Sok
authors.initials: MS
authors.lastname: Lee
authors.forename: Kee-Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Kim
authors.forename: William P
authors.initials: WP
authors.lastname: Tansey
authors.forename: Young
authors.initials: Y
authors.lastname: Do Yoo
mesh_terms: D002460:Cell Line; D016895:Culture Media, Serum-Free / Q000378:metabolism; D015536:Down-Regulation; D025461:Feedback, Physiological; D016193:G1 Phase; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D054875:Ubiquitination
chemical_list: D016895:Culture Media, Serum-Free; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D016271:Proto-Oncogene Proteins c-myc; C513338:ROMO1 protein, human; D017382:Reactive Oxygen Species; D044786:S-Phase Kinase-Associated Proteins