کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8324499 | 1539912 | 2012 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Proteasome deubiquitinases as novel targets for cancer therapy
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کلمات کلیدی
induced myeloid leukemia cell differentiation proteinTGF-ßBcl-xLDeubiquitinasesIκBHspUSPNOSBcl-2DeubiquitinaseDUBUbiquitin specific proteaseAMLAAA+ ATPasesATPases associated with diverse cellular activities - ATPases مرتبط با فعالیت های مختلف سلولیMcl1 - MCL1NFκB - NFKBROS - ROSBortezomib - بورتِـزومیبregulatory particle - ذرات مقرراتCancer - سرطانUbiquitin proteasome system - سیستم پروتئازوم Ubiquitinendoplasmic reticulum - شبکه آندوپلاسمی nuclear factor kappa-light-chain-enhancer of activated B cells - فاکتور هسته ای kappa-light-chain-enhancer از سلول های B فعال شده استB cell lymphoma 2 - لنفوم سلول B 2acute myeloid leukemia - لوسمی حاد میلوئیدی یا به اختصار AMLLysine - لیزینinhibitor of κB - مهار کننده κBMultiple myeloma - مولتیپل میلوماnitric oxide synthase - نیتریک اکسید سنتازProteasome - پروتئازومHeat shock protein - پروتئین شوک حرارتReactive oxygen species - گونههای فعال اکسیژنUPS - یو پی اسUbiquitin - یوبیکویتین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The ubiquitin-proteasome system (UPS) is a conserved pathway regulating numerous biological processes including protein turnover, DNA repair, and intracellular trafficking. Tumor cells are dependent on a functioning UPS, making it an ideal target for the development of novel anti-cancer therapies. The development of bortezomib (Velcade®) as a treatment for multiple myeloma and mantle cell lymphoma has verified this and suggests that targeting other components of the UPS may be a viable strategy for the treatment for cancer. We recently described a novel class of proteasome inhibitors that function by an alternative mechanism of action (D'Arcy et al., 2011). The small molecule b-AP15 blocks the deubiquitinase (DUB) activity of the 19S regulatory particle (19S RP) without inhibiting the proteolytic activities of the 20S core particle (20S CP). b-AP15 inhibits two proteasome-associated DUBs, USP14 and UCHL5, resulting in a rapid accumulation of high molecular weight ubiquitin conjugates and a functional proteasome shutdown. Interestingly, b-AP15 displays several differences to bortezomib including insensitivity to over-expression of the anti-apoptotic mediator Bcl-2 and anti-tumor activity in solid tumor models. In this review we will discuss the potential of proteasome deubiquitinase inhibitors as additions to the therapeutic arsenal against cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 44, Issue 11, November 2012, Pages 1729-1738
Journal: The International Journal of Biochemistry & Cell Biology - Volume 44, Issue 11, November 2012, Pages 1729-1738
نویسندگان
Pádraig D'Arcy, Stig Linder,