کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1951582 1055779 2007 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Adaptive modification and flexibility of the proteasome system in response to proteasome inhibition
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Adaptive modification and flexibility of the proteasome system in response to proteasome inhibition
چکیده انگلیسی

The highly conserved ubiquitin–proteasome system is the principal machinery for extralysosomal protein degradation in eukaryotic cells. The 26S proteasome, a large multicatalytic multisubunit protease that processes cell proteins by limited and controlled proteolysis, constitutes the central proteolytic component of the ubiquitin–proteasome system. By processing cell proteins essential for development, differentiation, proliferation, cell cycling, apoptosis, gene transcription, signal transduction, senescence, and inflammatory and stress response, the 26S proteasome plays a key role in the regulation and maintenance of basic cellular processes. Various synthetic and biologic inhibitors with different inhibitory profiles towards the proteolytic activities of the 26S proteasome have been identified recently. Such proteasome inhibitors induce apoptosis and cell cycle arrest preferentially in neoplastic cells. Based on these findings proteasome inhibitors became useful in cancer therapy. However, under the pressure of continuous proteasome inhibition, eukaryotic cells can develop complex adaptive mechanisms to subvert the lethal attack of proteasome inhibitors. Such mechanisms include the adaptive modification of the proteasome system with increased expression, enhanced proteolytic activity and altered subcomplex assembly and subunit composition of proteasomes as well as the expression of a giant oligomeric protease complex, tripeptidyl peptidase II, which partially compensates for impaired proteasome function. Here we review the adaptive mechanisms developed by eukaryotic cells in response to proteasome inhibition. These mechanisms reveal enormous flexibility of the proteasome system and may have implications in cancer biology and therapy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1773, Issue 9, September 2007, Pages 1389–1397
نویسندگان
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