Abstract
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 language | English |
|---|---|
| Pages (from-to) | 219-225 |
| Number of pages | 7 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 358 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2007 Jun 22 |
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Keywords
- Cyclin-dependent kinase inhibitor
- Degradation
- Nuclear export
- Reactive oxygen species
- Ubiquitination
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Cytoplasmic localization and ubiquitination of p21Cip1 by reactive oxygen species. / Hwang, Chae Young; Kim, Ick Young; Kwon, Ki Sun.
In: Biochemical and Biophysical Research Communications, Vol. 358, No. 1, 22.06.2007, p. 219-225.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cytoplasmic localization and ubiquitination of p21Cip1 by reactive oxygen species
AU - Hwang, Chae Young
AU - Kim, Ick Young
AU - Kwon, Ki Sun
PY - 2007/6/22
Y1 - 2007/6/22
N2 - 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.
AB - 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.
KW - Cyclin-dependent kinase inhibitor
KW - Degradation
KW - Nuclear export
KW - Reactive oxygen species
KW - Ubiquitination
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UR - http://www.scopus.com/inward/citedby.url?scp=34248161671&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2007.04.120
DO - 10.1016/j.bbrc.2007.04.120
M3 - Article
VL - 358
SP - 219
EP - 225
JO - The BMJ
JF - The BMJ
SN - 0730-6512
IS - 1
ER -