کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1964877 | 1058628 | 2008 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pam (Protein associated with Myc) functions as an E3 Ubiquitin ligase and regulates TSC/mTOR signaling
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
PBSrpm-1DPTRHDHEK293TUBCTSCPAMmTORRNA interference - RNA تداخل کنندهRNAi - RNA سرکوبگر،RNA مداخلهگر، RNA خاموش کنندهRing finger - انگشت انگشتImmunoprecipitation - تخریب ایمنیTuberin - توبیرینDIV - دیوdays in vitro - روز in vitroPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریmammalian target of rapamycin - هدف پستانداران رپامایسینHamartin - همارتینWestern blotting - وسترن بلاتینگTuberous sclerosis complex - کمپلکس توبروس اسکلروزیسubiquitination - یوبی کوئیتینه شدن Ubiquitin - یوبیکویتین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The tumor suppressor tuberin, encoded by the Tuberous Sclerosis Complex (TSC) gene TSC2, negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in the control of cell growth and proliferation. In addition to naturally occurring mutations, several kinases including Akt, RSK1, and ERK are known to phosphorylate and inactivate tuberin. We demonstrate a novel mechanism of tuberin inactivation through ubiquitination by Pam, a putative RING finger-containing E3 ubiquitin (Ub) ligase in mammalian cells. We show that Pam associates with E2 ubiquitin-conjugating enzymes, and tuberin can be ubiquitinated by Pam through its RING finger domain. Tuberin ubiquitination is independent of its phosphorylation by Akt, RSK1, and ERK kinases. Pam is also self-ubiquitinated through its RING finger domain. Moreover, the TSC1 protein hamartin, which forms a heterodimer with tuberin, protects tuberin from ubiquitination by Pam. However, TSC1 fails to protect a disease-associated missense mutant of TSC2 from ubiquitination by Pam. Furthermore, Pam knockdown by RNA interference (RNAi) in rat primary neurons elevates the level of tuberin, and subsequently inhibits the mTOR pathway. Our results provide novel evidence that Pam can function as an E3 Ub ligase toward tuberin and regulate mTOR signaling, suggesting that Pam can in turn regulate cell growth and proliferation as well as neuronal function through the TSC/mTOR pathway in mammalian cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 20, Issue 6, June 2008, Pages 1084-1091
Journal: Cellular Signalling - Volume 20, Issue 6, June 2008, Pages 1084-1091
نویسندگان
Sangyeul Han, Rochelle M. Witt, Túlio M. Santos, Carolyn Polizzano, Bernardo L. Sabatini, Vijaya Ramesh,