کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1963622 1058482 2012 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
CK2 regulates ATF4 and CHOP transcription within the cellular stress response signalling pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
CK2 regulates ATF4 and CHOP transcription within the cellular stress response signalling pathway
چکیده انگلیسی

Protein kinase CK2 is an ubiquitously expressed serine/threonine kinase. The protein levels along with CK2 activity are highly elevated in tumour cells where it protects cells from apoptosis. Accordingly, inhibition of CK2 is known to induce programmed cell death, making it a promising target for cancer therapy. Analysis of the different behaviour of hormone sensitive LNCaP cells and hormone refractory PC-3 cells after CK2 inhibition revealed CHOP ((C/EBP)-homologous protein) induction and therefore probably ER stress as crucial for apoptosis in the LNCaP cells. In the present study we investigated which promoter element of the CHOP promoter is responsible for its induction. ER stress can be generated by the accumulation of unfolded proteins, by depletion of amino acids or by oxidative stress. ER stress induces specific signalling pathways. In order to analyse which pathway might be activated by CK2 inhibition we started to analyse the activation of the different CHOP promoter elements. By using mutated reporter constructs of the CHOP promoter, it turned out that the amino acid response element (AARE) is the most prominent element for CHOP induction after CK2 inhibition. The ER stress element, however, proves to be less crucial, and along with the AP-1 binding site, they do not seem to play any role. Further we found an up-regulation of the transcription factor ATF4 after CK2 inhibition. ATF4 is involved in ER stress signalling through the AARE, which further supports our finding that CK2 inhibition provokes an amino acid induced response pathway.


► CK2 inhibition induces CHOP transcription in hormone dependent PCA cells.
► CHOP transcription is induced via the amino acid response element in the promoter.
► AP-1 binding site and ER stress element seem to be less crucial for transcription.
► The activating transcription factor 4 (ATF4) is responsible for the CHOP induction.
► ATF4 protein level is up-regulated in a post-transcriptional way by CK2 inhibition.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 24, Issue 9, September 2012, Pages 1797–1802
نویسندگان
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