کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2563543 1560952 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Expression, function, and targeting of the nuclear exporter chromosome region maintenance 1 (CRM1) protein
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Expression, function, and targeting of the nuclear exporter chromosome region maintenance 1 (CRM1) protein
چکیده انگلیسی

Nucleocytoplasmic trafficking of proteins/RNAs is essential to normal cellular function. Indeed, accumulating evidence suggests that cancer cells escape anti-neoplastic mechanisms and benefit from pro-survival signals via the dysregulation of this system. The nuclear exporter chromosome region maintenance 1 (CRM1) protein is the only protein in the karyopherin-β protein family that contributes to the trafficking of numerous proteins and RNAs from the nucleus. It is considered to be an oncogenic, anti-apoptotic protein in transformed cells, since it reportedly functions as a gatekeeper for cell survival, including affecting p53 function, and ribosomal biogenesis. Furthermore, abnormally high expression of CRM1 is correlated with poor patient prognosis in various malignancies. Therapeutic targeting of CRM1 has emerged as a novel cancer treatment strategy, starting with a clinical trial with leptomycin B, the original specific inhibitor of CRM1, followed by development of several next-generation small molecules. KPT-330, a novel member of the CRM1-selective inhibitors of nuclear export (SINE) class of compounds, is currently undergoing clinical evaluation for the therapy of various malignancies. Results from these trials suggest that SINE compounds may be particularly useful against hematological malignancies, which often become refractory to standard chemotherapeutic agents.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacology & Therapeutics - Volume 153, September 2015, Pages 25–35
نویسندگان
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