کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8478670 | 1551149 | 2013 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
C-terminal binding proteins are essential pro-survival factors that undergo caspase-dependent downregulation during neuronal apoptosis
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کلمات کلیدی
CGNsMTOBmESCsCtBPBCL-3DGCR8PARPMEFsDAPIRSS6-HydroxydopamineSTS6-OHDAPBSINVCCDMPP+ - MPP +micro RNA - RNA میکروNeuronal apoptosis - آپوپتوز عصبیstaurosporine - استوسوسورپینactinomycin D - اکتینومایسین Dcon - باtoxin B - توکسین BCharge-Coupled Device - دستگاه متصل شارژRNA silencing suppressor - سرکوب کننده خاموش کننده RNAMouse embryonic stem cells - سلول های بنیادی جنینی موشLethal toxin - سمی کشندهanti - ضدphosphate buffer saline - فسفات بافر شورmurine embryonic fibroblasts - فیبروبلاست های جنینی جنینیInverse - معکوسMiRNA - میکروRNA، ریزآرانای، miRNAknockout - ناکاوتcerebellar granule neurons - نورونهای گرانشی مخچهwild type - نوع وحشیsodium nitroprusside - نیتروپروساید سدیمpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازC-terminal binding protein - پروتئین اتصال دهنده انتهایی Cpoly-(ADP-ribose) polymerase - پلیمراز (ADP-ribose) پلیمرازSNP - چندریختی تک-نوکلئوتیدCaspase-3 - کاسپاز ۳ Control - کنترل
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: C-terminal binding proteins are essential pro-survival factors that undergo caspase-dependent downregulation during neuronal apoptosis C-terminal binding proteins are essential pro-survival factors that undergo caspase-dependent downregulation during neuronal apoptosis](/preview/png/8478670.png)
چکیده انگلیسی
C-terminal binding proteins (CtBPs) are transcriptional co-repressors that are subject to proteasome-dependent downregulation during apoptosis. Alternative mechanisms that regulate CtBP expression are currently under investigation and the role of CtBPs in neuronal survival is largely unexplored. Here, we show that CtBPs are downregulated in cerebellar granule neurons (CGNs) induced to undergo apoptosis by a variety of stressors. Moreover, antisense-mediated downregulation of CtBP1 is sufficient to cause CGN apoptosis. Similarly, the CtBP inhibitor, 4-methylthio-2-oxobutyric acid, induces expression of the CtBP target Noxa and causes actinomycin-sensitive CGN apoptosis. Unexpectedly, we found that the mechanism of CtBP downregulation in CGNs undergoing apoptosis varies in a stimulus-specific manner involving either the proteasome or caspases. In the case of CGNs deprived of depolarizing potassium (5K apoptotic condition), caspases appear to play a dominant role in CtBP downregulation. However, incubation in 5K does not enhance the kinetics of CtBP1 degradation and recombinant CtBP1 is not cleaved in vitro by caspase-3. In addition, 5K has no significant effect on CtBP transcript expression. Finally, mouse embryonic stem cells display caspase-dependent downregulation of CtBP1 following exposure to staurosporine, an effect that is not observed in DGCR8 knockout cells which are deficient in miRNA processing. These data identify caspase-dependent downregulation of CtBPs as an alternative mechanism to the proteasome for regulation of these transcriptional co-repressors in neurons undergoing apoptosis. Moreover, caspases appear to regulate CtBP expression indirectly, at a post-transcriptional level, and via a mechanism that is dependent upon miRNA processing. We conclude that CtBPs are essential pro-survival proteins in neurons and their downregulation contributes significantly to neuronal apoptosis via the de-repression of pro-apoptotic genes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Neuroscience - Volume 56, September 2013, Pages 322-332
Journal: Molecular and Cellular Neuroscience - Volume 56, September 2013, Pages 322-332
نویسندگان
Trisha R. Stankiewicz, Emily K. Schroeder, Natalie A. Kelsey, Ron J. Bouchard, Daniel A. Linseman,