Romo1 is a negative-feedback regulator of Myc
  • Lee, Seung Baek
  • Kim, Jung Jin
  • Chung, Jin Sil
  • Lee, Myeong-Sok
  • Lee, Kee-Ho
  • 외 3명
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초록

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.

키워드

MycRomo1ROSSkp2F-BOX PROTEINUBIQUITIN-MEDIATED PROTEOLYSISGLYCOGEN-SYNTHASE KINASE-3CELL-CYCLE PROGRESSIONC-MYCOXIDATIVE STRESSROS PRODUCTIONPHOSPHORYLATIONDEGRADATIONSKP2
제목
Romo1 is a negative-feedback regulator of Myc
저자
Lee, Seung BaekKim, Jung JinChung, Jin SilLee, Myeong-SokLee, Kee-HoKim, Byung SooTansey, William P.Yoo, Young Do
DOI
10.1242/jcs.079996
발행일
2011-06
유형
Article
저널명
Journal of Cell Science
124
11
페이지
1911 ~ 1924