کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8455313 | 1548021 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Reprint of: Decorin activates AMPK, an energy sensor kinase, to induce autophagy in endothelial cells
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کلمات کلیدی
AMPKPEG3IR-AVps34ULK1RTKSLRPHUVECmTORProliferation - ترویجdecorin - دکورینHuman umbilical vein endothelial cells - سلول های اندوتلیالی ورید ناف انسانSignaling - سیگنالینگmammalian target of rapamycin - هدف پستانداران رپامایسینsmall leucine-rich proteoglycan - پروتئگلیکان غنی از لوسین است5′ adenosine monophosphate-activated protein kinase - پروتئین کیناز فعال شده با آدنوزین مونوفسفات 5 'Receptor Tyrosine Kinase - گیرنده تیروزین کیناز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The highly conserved eukaryotic process of macroautophagy (autophagy) is a non-specific bulk-degradation program critical for maintaining proper cellular homeostasis, and for clearing aged and damaged organelles. This decision is inextricably dependent upon prevailing metabolic demands and energy requirements of the cell. Soluble monomeric decorin functions as a natural tumor repressor that antagonizes a variety of receptor tyrosine kinases. Recently, we discovered that decorin induces endothelial cell autophagy, downstream of VEGFR2. This process was wholly dependent upon Peg3, a decorin-inducible genomically imprinted tumor suppressor gene. However, the signaling cascades responsible have remained elusive. In this report we discovered that Vps34, a class III phosphoinositide kinase, is an upstream kinase required for Peg3 induction. Moreover, decorin triggered differential formation of Vps34/Beclin 1 complexes with concomitant dissolution of inhibitive Bcl-2/Beclin 1 complexes. Further, decorin inhibited anti-autophagic signaling via suppression of Akt/mTOR/p70S6K activity with the concurrent activation of pro-autophagic AMPK-mediated signaling cascades. Mechanistically, AMPK is downstream of VEGFR2 and inhibition of AMPK signaling abrogated decorin-evoked autophagy. Collectively, these findings hint at the complexity of the underlying molecular relays necessary for decorin-evoked endothelial cell autophagy and reveal important therapeutic targets for augmenting autophagy and combatting tumor angiogenesis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Matrix Biology - Volume 35, April 2014, Pages 42-50
Journal: Matrix Biology - Volume 35, April 2014, Pages 42-50
نویسندگان
Atul Goyal, Thomas Neill, Rick T. Owens, Liliana Schaefer, Renato V. Iozzo,