کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10816025 | 1058535 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Reduced phosphorylation of Stat3 at Ser-727 mediated by casein kinase 2 - Protein phosphatase 2A enhances Stat3 Tyr-705 induced tumorigenic potential of glioma cells
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کلمات کلیدی
PBSGBMCK2WCLqRT-PCRPP2ACPCSEASTAT3FACSSDS-PAGE - الکتروفورز ژل پلی آکریل آمیدSodium dodecyl sulfate polyacrylamide gel electrophoresis - الکتروفورز ژل پلی اتیل آمید سدیم دودسیل سولفاتempty vector - بردار خالیImmunoprecipitation - تخریب ایمنیRoom temperature - دمای اتاقPhosphate buffered saline - فسفات بافر شورfluorescence activated cell sorting - فلورسانس سلول فعال فعال سلولwhole cell lysate - لسیات کل سلولsignal transducer and activator of transcription 3 - مبدل سیگنال و فعال کننده رونویسی 3quantitative real time polymerase chain reaction - واکنش زنجیره ای پلیمراز واقعی در زمان واقعیprotein phosphatase 2A - پروتئین فسفاتاز 2APropidium iodide - پروتئین یدیدCasein kinase 2 - کازئین کیناز 2Glioblastoma multiforme - گلیوبلاستوم مولتیفرم، گلیوبلاستوماGlioma - گلیوما
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is involved in cell survival and proliferation and has been found to be persistently activated in most human cancers mainly through its phosphorylation at Tyr-705. However, the role and regulation of Stat3 Ser-727 phosphorylation in cancer cells have not been clearly evaluated. In our findings, correlation studies on the expression of CK2 and Stat3 Ser-727 phosphorylation levels in human glioma patient samples as well as rat orthotopic tumor model show a degree of negative correlation. Moreover, brain tumor cell lines were treated with various pharmacological inhibitors to inactivate the CK2 pathway. Here, increased Stat3 Ser-727 phosphorylation upon CK2 inhibition was observed. Overexpression of CK2 (α, αⲠor β subunits) by transient transfection resulted in decreased Stat3 Ser-727 phosphorylation. Stat3 Tyr-705 residue was conversely phosphorylated in similar situations. Interestingly, we found PP2A, a protein phosphatase, to be a mediator in the negative regulation of Stat3 Ser-727 phosphorylation by CK2. In vitro assays prove that Ser-727 phosphorylation of Stat3 affects the transcriptional activity of its downstream targets like SOCS3, bcl-xl and Cyclin D1. Stable cell lines constitutively expressing Stat3 S727A mutant showed increased survival, proliferation and invasion which are characteristics of a cancer cell. Rat tumor models generated with the Stat3 S727A mutant cell line formed more aggressive tumors when compared to the Stat3 WT expressing stable cell line. Thus, in glioma, reduced Stat3 Ser-727 phosphorylation enhances tumorigenicity which may be regulated in part by CK2-PP2A pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 26, Issue 8, August 2014, Pages 1725-1734
Journal: Cellular Signalling - Volume 26, Issue 8, August 2014, Pages 1725-1734
نویسندگان
Tapashi Mandal, Arijit Bhowmik, Anirban Chatterjee, Uttara Chatterjee, Sandip Chatterjee, Mrinal Kanti Ghosh,