کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10802163 | 1055663 | 2014 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Phosphorylation of p300 increases its protein degradation to enhance the lung cancer progression
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
p300 is a transcription cofactor for a number of nuclear proteins. Most studies of p300 have focused on the regulation of its function, which primarily includes its role as a transcription co-factor for a number of nuclear proteins. In this study, we found that p300 was highly phosphorylated and its level was decreased during mitosis and tumorigenesis. In vitro and in vivo experiments aimed showed that cyclin-dependent kinase 1 (CDK1) and ERK1/2 phosphorylated p300 on Ser1038 and Ser2039. Mutations of Ser1038 and Ser2039 increased p300 protein stability and levels. Inhibition of p300 degradation by blocking its phosphorylation decreased the proliferation and metastasis activity of lung cancer cells, indicating that p300 acts as a tumor suppressor in lung cancer tumorigenesis. Investigation of the molecular mechanism showed that blocking p300 phosphorylation disrupted chromatin condensation and the increased the acetylation of histone H3. Analysis of cell cycle progression in HA-p300-S2A-expressing cells by flow cytometry showed that the p300 mutants arrested the cells at S-phase or delayed the mitotic entry and exit. The expression of several important oncogenes, MMP-9, vimentin, β-catenin, N-cadherin and c-myc, was negatively regulated by p300. In conclusion, during lung tumorigenesis, a phosphorylation-mediated decrease in p300 level enhanced oncogene expression during interphase and decreased histone H3 acetylation during mitosis, which promoted lung cancer progression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1843, Issue 6, June 2014, Pages 1135-1149
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1843, Issue 6, June 2014, Pages 1135-1149
نویسندگان
Shao-An Wang, Chia-Yang Hung, Jian-Ying Chuang, Wen-Chang Chang, Tsung-I Hsu, Jan-Jong Hung,