کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2101018 | 1546210 | 2010 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Dissecting the transcriptional functions of human DNA topoisomerase I by selective inhibitors: Implications for physiological and therapeutic modulation of enzyme activity
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Camptothecin is a selective inhibitor of DNA topoisomerase I, and has effective antitumor activity. Recently, camptothecin has been shown to activate the transcription of low-abundance antisense RNAs at the HIF-1α gene locus in human cancer cells in a Topoisomerase I-dependent manner. The activation of antisense transcription is likely due to sustained drug interference with transcription regulation mechanisms leading to a more open chromatin conformation and de-repression/activation of antisense transcription. Camptothecin readily inhibits Topoisomerase I in cells, and the enzyme inhibition activates transcriptional Cdk (Cdk9 and/or Cdk7) activity leading to the hyperphosphorylation of the CTD of the largest subunit of RNA polymerase II (RNAP II). This results in an alteration of RNAP II regulation with specific effects at transcription levels. Thus, the findings have documented that camptothecin can interfere with specific transcription regulatory steps, impairing the balance of cellular antisense and sense transcripts at the HIF-1α gene locus. That may have a considerable impact on cancer therapy development particularly for non-responsive human tumors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer - Volume 1806, Issue 2, December 2010, Pages 240-250
Journal: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer - Volume 1806, Issue 2, December 2010, Pages 240-250
نویسندگان
Giovanni Capranico, Jessica Marinello, Laura Baranello,