کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1980382 | 1061849 | 2012 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The HDAC inhibitor depsipeptide transactivates the p53/p21 pathway by inducing DNA damage
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کلمات کلیدی
TSAHDACiCK1TrxTrxRCATDNA-PKPTMsATRGRxDepsipeptideATM- and Rad3-relatedp53HDACsCHK2VRK1l-NACROS - ROSAra-C - آرا- CDNA damage - آسیبDNAthioredoxin reductase - تریودوکسین ردوکتازTrichostatin - تریکوستاتینpost-translational modifications - تغییرات پس از ترجمه، پیرایش پساترجمهthioredoxin - تیرودوکسینATM - خودپردازdihydroethidium - دی هیدروتیدیمSOD - سدSuperoxide dismutase - سوکسوکس دیسموتازcytarabine - سیتارابینHDAC inhibitors - مانع از HDAChistone deacetylases - هیستون deacetylaseshistone acetyltransferases - هیستون استیل ترانسفرازDHE - وCatalase - کاتالازcasein kinase 1 - کازئین کیناز 1HAT - کلاهGlutaredoxin - گلوتاراکسینReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Histone deacetylase (HDAC) inhibitors have been proven to be effective therapeutic agents to kill cancer cells through inhibiting HDAC activity or altering the structure of chromatin. As a potent HDAC inhibitor, depsipeptide not only modulates histone deacetylation but also activates non-histone protein p53 to inhibit cancer cell growth. However, the mechanism of depsipeptide-induced p53 transactivity remains unknown. Here, we show that depsipeptide causes DNA damage through induction of reactive oxygen species (ROS) generation, as demonstrated by a comet assay and by detection of the phosphorylation of H2AX. Depsipeptide induced oxidative stress was confirmed to relate to a disturbance in reduction-oxidation (redox) reactions through inhibition of the transactivation of thioredoxin reductase (TrxR) in human cancer cells. Upon treatment with depsipeptide, p53 phosphorylation at threonine 18 (Thr18) was specifically induced. Furthermore, we also demonstrated that phosphorylation of p53 at Thr18 is required for p53 acetylation at lysine 373/382 and for p21 expression in response to depsipeptide treatment. Our results demonstrate that depsipeptide plays an anti-neoplastic role by generating ROS to elicit p53/p21 pathway activation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 11, Issue 2, 1 February 2012, Pages 146-156
Journal: DNA Repair - Volume 11, Issue 2, 1 February 2012, Pages 146-156
نویسندگان
Haiying Wang, Wen Zhou, Zhixing Zheng, Ping Zhang, Bo Tu, Qihua He, Wei-Guo Zhu,