کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6022220 | 1580666 | 2013 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Prion formation correlates with activation of translation-regulating protein 4E-BP and neuronal transcription factor Elk1
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کلمات کلیدی
U0126p70 ribosomal S6 Kinase 1bromodeoxiuridineGT1-1 cellsPrPscPrPc4E-BPmTORC1eIF4ES6K1TSCERKBDNF - BDNF یا فاکتور نورونزایی مشتقشده از مغز DMSO - DMSOBrdU - بروموداکسی اوریدینNeurodegenerative diseases - بیماری های نوروژنیکDimethyl sulfoxide - دیمتیل سولفواکسیدNervous system - سیستم عصبیIntracellular signaling - سیگنال درون سلولیeukaryotic initiation factor 4E - عامل آغاز کننده یوکاریوتی 4EInfections - عفونت هاBrain-derived neurotrophic factor - فاکتور نوروتروفی مشتق شده از مغزleupeptin - لئوپتینMEK - مجاهدین خلقmap - نقشهMammalian target of rapamycin complex 1 - هدف پستانداران مجتمع رپامایسین 1Ribosomal protein S6 - پروتئین Ribosomal S6mitogen-activated protein - پروتئین فعال mitogenmitogen-activated protein kinase kinase - پروتئین کیناز کیناز فعال Mitogen فعالPrions - پریون هاTuberous sclerosis complex - کمپلکس توبروس اسکلروزیسextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Prion formation correlates with activation of translation-regulating protein 4E-BP and neuronal transcription factor Elk1 Prion formation correlates with activation of translation-regulating protein 4E-BP and neuronal transcription factor Elk1](/preview/png/6022220.png)
چکیده انگلیسی
Cellular mechanisms play a role in conversion of the normal prion protein PrPC to the disease-associated protein PrPSc. The cells provide not only PrPC, but also still largely undefined factors required for efficient prion replication. Previously, we have observed that interference with ERK and p38-JNK MAP kinase pathways has opposing effects on the formation of prions indicating that the process is regulated by a balance in intracellualar signaling pathways. In order to obtain a “flow-chart” of such pathways, we here studied the activation of MEK/ERK and mTORC1 downstream targets in relation to PrPSc accumulation in GT1-1 cells infected with the RML or 22L prion strains. We show that inhibition of mTORC1 with rapamycin causes a reduction of PrPSc accumulation at similar low levels as seen when the interaction between the translation initiation factors eIF4E and eIF4G downstream mTORC1 is inhibited using 4EGI-1. No effect is seen following the inhibition of molecules (S6K1 and Mnk1) that links MEK/ERK signaling to mTORC1-mediated control of translation. Instead, stimulation (high [KCl] or [serum]) or inhibition (MEK-inhibitor) of prion formation is associated with increased or decreased phosphorylation of the neuronal transcription factor Elk1, respectively. This study shows that prion formation can be modulated by translational initiating factors, and suggests that MEK/ERK signaling plays a role in the conversion of PrPC to PrPSc via an Elk1-mediated transcriptional control. Altogether, our studies indicate that prion protein conversion is under the control of intracellular signals, which hypothetically, under certain conditions may elicit irreversible responses leading to progressive neurodegenerative diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 58, October 2013, Pages 116-122
Journal: Neurobiology of Disease - Volume 58, October 2013, Pages 116-122
نویسندگان
Elin K. Allard, Mirjana Grujic, Gilberto Fisone, Krister Kristensson,