Romo1 is a negative-feedback regulator of Myc

Seung Baek Lee, Jung Jin Kim, Jin Sil Chung, Myeong Sok Lee, Kee Ho Lee, Byung Soo Kim, William P. Tansey, Young Do Yoo

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Degradation of Myc protein is mediated by E3 ubiquitin ligases, including SCFFbw7 and SCFSkp2, 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.

Original languageEnglish
Pages (from-to)1911-1924
Number of pages14
JournalJournal of Cell Science
Volume124
Issue number11
DOIs
Publication statusPublished - 2011 Jun 1

Keywords

  • Myc
  • ROS
  • Romo1
  • Skp2

ASJC Scopus subject areas

  • Cell Biology

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    Lee, S. B., Kim, J. J., Chung, J. S., Lee, M. S., Lee, K. H., Kim, B. S., Tansey, W. P., & Yoo, Y. D. (2011). Romo1 is a negative-feedback regulator of Myc. Journal of Cell Science, 124(11), 1911-1924. https://doi.org/10.1242/jcs.079996