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Nucleocytoplasmic translocation and ubiquitin‐dependent degradation of p21Cip1 by reactive oxygen species
Author(s) -
Hwang Chae Young,
Kim Ick Young,
Kwon KiSun
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb13
Subject(s) - microbiology and biotechnology , cell cycle , proteasome , nuclear export signal , chemistry , protein degradation , reactive oxygen species , biochemistry , ubiquitin , cell , biology , cell nucleus , cytoplasm , gene
p21Cip1 inhibits cell cycle progression via direct binding with cyclin‐dependent kinase and proliferating cell nuclear antigen. Here we show that p21Cip1 is degraded at an early phase after treating a variety of cell types with low but not high doses of H2O2. Preincubation of cells with an antioxidant N‐acetyl cysteine prevented this p21Cip1 degradation. A mutant p21Cip1 in which all six lysines were changed to arginine was stable against H2O2 treatment. Proteasome inhibitors rescued H2O2‐induced p21Cip1 degradation. These results together indicate an ubiquitin‐dependent proteasome pathway. Disruption of the nuclear export signal sequence in p21Cip1 or leptomycin B treatment blocked the H2O2‐induced p21Cip1 degradation, indicating requirements of nucleocytoplasmic translocation of p21Cip1 before degradation. We suggest that p21Cip1 degradation is a possible mechanism involved in cell cycle control by reactive oxygen species.