RRC ID 42177
著者 Ishii T, Fujishiro M, Masuda M, Goshima Y, Kitamura H, Teramoto S, Matsuse T.
タイトル Effects of p27Kip1 on cell cycle status and viability in A549 lung adenocarcinoma cells.
ジャーナル Eur Respir J
Abstract p27Kip1 is a cyclin-dependent kinase inhibitor, it negatively regulates G1 progression and is reported to modulate apoptosis. Phosphorylation of this protein is thought to regulate its intracellular localisation and affect its stability. The aim of this study was to regulate p27Kip1 expression levels, and to examine how this protein affects cell cycle status and modulates viability in A549 lung adenocarcinoma cells. In addition, the association between phosphorylation status of p27Kip1 and its intracellular localisation was investigated, using expression vectors with cDNA of p27Kip1 or mutants in which the phosphorylation sites had been mutated. Although overexpression of p27Kip1 reduced cell cycle progression, its removal did not change cell cycle status. Modest induction of p27Kip1 rescued adenovector-induced apoptosis and its removal with short interfering RNA increased spontaneous cell death. It was also observed that p27Kip1 localised mainly in the cytoplasm, and forced expression of p27Kip1 cDNA with the substitution of serine (S) 10, threonine (T) 157 and T198 to glutamate (phosphor-mimetic) induced its cytoplasmic localisation. In conclusion, p27Kip1, when expressed physiologically, exists mainly in the cytoplasm, has little effect on cell cycle status and contributes viability in A549 lung adenocarcinoma cells. It was also surmised that intracellular localisation of p27Kip1 dominates its function and that its localisation was partly determined by its phosphorylation.
巻・号 23(5)
ページ 665-70
公開日 2004-5-1
DOI 10.1183/09031936.04.00096204
PMID 15176677
MeSH Adenocarcinoma / pathology* Adenocarcinoma / physiopathology* Amino Acid Substitution Apoptosis Cell Cycle* Cell Cycle Proteins / antagonists & inhibitors Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cell Line Cell Survival Cyclin-Dependent Kinase Inhibitor p27 Cytoplasm / metabolism Enzyme Inhibitors / metabolism* Glutamic Acid Humans Lung Neoplasms / pathology* Lung Neoplasms / physiopathology* Phosphorylation Serine Threonine Tissue Distribution Tumor Suppressor Proteins / antagonists & inhibitors Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism*
IF 12.339
引用数 15
WOS 分野 RESPIRATORY SYSTEM
リソース情報
ヒト・動物細胞