کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815267 | 1058462 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The β-catenin E3 ubiquitin ligase SIAH-1 is regulated by CSN5/JAB1 in CRC cells
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کلمات کلیدی
SCFSIAH-1CSN5/Jab1CSN5Jab1NEDD8CSNCRLSIPWntSkp1CK1CUL1AP-1GSK-3βAPCTCFMPNadenomatous polyposis coli - آدنوماتوز پولیپوزیس کولی یا آدنوماتوس پولیپوزیس کولای Jamm - آرهβ-catenin - بتا-کاتنینColorectal cancer - سرطان روده بزرگCOP9 signalosome - سیگنال COP9lymphoid enhancer factor - عامل افزایش دهنده لنفاویT cell factor - عامل سلول TLef - لفWnt pathway - مسیر WntCo-Immunoprecipitation - هم ایمن زداییCoIP - همکاری کنیدactivator protein-1 - پروتئین فعال کننده-1casein kinase 1 - کازئین کیناز 1CRC - کد افزونگی دورهای Glycogen synthase kinase-3β - گلیکوزین سنتاز کیناز 3β
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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![عکس صفحه اول مقاله: The β-catenin E3 ubiquitin ligase SIAH-1 is regulated by CSN5/JAB1 in CRC cells The β-catenin E3 ubiquitin ligase SIAH-1 is regulated by CSN5/JAB1 in CRC cells](/preview/png/10815267.png)
چکیده انگلیسی
COP9 signalosome subunit 5 (CSN5) plays a decisive role in cellular processes such as cell cycle regulation and apoptosis via promoting protein degradation, gene transcription, and nuclear export. CSN5 regulates cullin-RING-E3 ligase (CRL) activity through its deNEDDylase function. It is overexpressed in several tumor entities, but its role in colorectal cancer (CRC) is poorly understood. Wnt/β-catenin signaling is aberrant in most CRC cells, resulting in increased levels of oncogenic β-catenin and thus tumor progression. Under physiological conditions, β-catenin levels are tightly regulated by continuous proteasomal degradation. We recently showed that knockdown of CSN5 in model and CRC cells results in decreased (phospho)-β-catenin levels. Reduced β-catenin levels were associated with an attenuated proliferation rate of different CRC cell types after CSN5 knockdown. The canonical Wnt pathway involves degradation of β-catenin by a β-TrCP1-containing E3 ligase, but is mostly non-functional in CRC cells. We thus hypothesized that alternative β-catenin degradation mediated by SIAH-1 (seven in absentia homolog-1), is responsible for the effect of CSN5 on β-catenin signaling in CRC cells. We found that SIAH-1 plays an essential role in β-catenin degradation in HCT116 CRC cells and that CSN5 affects β-catenin target gene expression in these cells. Of note, CSN5 affected SIAH-1 mRNA and SIAH-1 protein levels. Moreover, β-catenin and SIAH-1 form protein complexes with CSN5 in HCT116 cells. Lastly, we demonstrate that CSN5 promotes SIAH-1 degradation in HCT116 and SW480 cells and that this is associated with its deNEDDylase activity. In conclusion, we have identified a CSN5/β-catenin/SIAH-1 interaction network that might control β-catenin degradation in CRC cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 26, Issue 9, September 2014, Pages 2051-2059
Journal: Cellular Signalling - Volume 26, Issue 9, September 2014, Pages 2051-2059
نویسندگان
Sandra Jumpertz, Thomas Hennes, Yaw Asare, Jörg Vervoorts, Jürgen Bernhagen, Anke K. Schütz,