Cytoplasmic localization and ubiquitination of p21Cip1 by reactive oxygen species

Chae Young Hwang, Ick Young Kim, Ki Sun Kwon

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


Reactive oxygen species were previously shown to trigger p21Cip1 protein degradation through a proteasome-dependent pathway, however the detailed mechanism of degradation remains to be elucidated. In this report, we showed that p21Cip1 was degraded at an early phase after low dose H2O2 treatment of a variety of cell types and that preincubation of cells with the antioxidant, N-acetylcysteine, prolonged p21Cip1 half-life. A mutant p21Cip1 in which all six lysines were changed to arginines was protected against H2O2 treatment. Direct interaction between p21Cip1 and Skp2 was elevated in the H2O2-treated cells. Disruption of the two nuclear export signal (NES) sequences in p21Cip1, or treatment with leptomycin B blocked H2O2-induced p21Cip1 degradation. Altogether, these results demonstrate that reactive oxygen species induce p21Cip1 degradation through an NES-, Skp2-, and ubiquitin-dependent pathway.

Original languageEnglish
Pages (from-to)219-225
Number of pages7
JournalBiochemical and biophysical research communications
Issue number1
Publication statusPublished - 2007 Jun 22

Bibliographical note

Funding Information:
This work was supported by Grant from MOST, KOSEF, KRF, and KRIBB. We thank Michele Pagano and Rati Fotedar for the kind gift of p21 Cip1 constructs, Harvey Ozer for ts20TG R cells, Jae-Ryong Kim for HDF, and Yeon-Soo Seo for Skp2 construct. We thank Dae-Sik Lim for helpful discussion.

Copyright 2008 Elsevier B.V., All rights reserved.


  • Cyclin-dependent kinase inhibitor
  • Degradation
  • Nuclear export
  • Reactive oxygen species
  • Ubiquitination

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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