کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10902369 | 1084747 | 2015 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Suggestive evidence on the involvement of polypyrimidine-tract binding protein in regulating alternative splicing of MAP/microtubule affinity-regulating kinase 4 in glioma
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کلمات کلیدی
EMSAUSP5FGFR-1ISSGBMhnRNPPKMIVSPTBintronic splicing silencerElectrophoretic mobility shift assay - آزمون تحرک تحرک الکتروفورزAlternative splicing - جابجایی جایگزینintervening sequence - دنباله مداخلهRON - رونheterogeneous nuclear ribonucleoprotein - ریبونولوپروتئین ناهمگن هسته ایMass spectrometry - طیف سنجی جرمیGlioblastoma - گلیوبلاستوماGlioma - گلیوما Fibroblast growth factor receptor-1 - گیرنده فاکتور رشد فیبروبلاست 1
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
Bioinformatic analysis revealed four putative polypyrimidine-tract binding (PTB) protein binding sites in MARK4 introns 15 and 16. Glioma tissues and glioblastoma-derived cancer stem cells showed, compared with normal brain, significant overexpression of PTB, correlated with high MARK4L mRNA expression. Splicing minigene assays revealed a functional intronic splicing silencer in MARK4 intron 15, but mutagenesis of the PTB binding site in this region did not affect minigene splicing, suggesting that PTB may bind to a splicing silencer other than the predicted one and synergistically acting with the other predicted PTB sites. Electrophoretic mobility shift assays coupled with mass spectrometry confirmed binding of PTB to the polypyrimidine tract of intron 15, and thus its involvement in MARK4 alternative splicing. This finding, along with evidence of PTB overexpression in gliomas and glioblastoma-derived cancer stem cells and differentiated progeny, merged in pointing out the involvement of PTB in the switch to MARK4L, consistent with its established role in driving oncogenic splicing in brain tumors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 359, Issue 1, 1 April 2015, Pages 87-96
Journal: Cancer Letters - Volume 359, Issue 1, 1 April 2015, Pages 87-96
نویسندگان
L. Fontana, D. Rovina, C. Novielli, E. Maffioli, G. Tedeschi, I. Magnani, L. Larizza,