کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8311353 1538660 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mechanisms of p53 degradation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Mechanisms of p53 degradation
چکیده انگلیسی
The tumor suppressor p53 plays various functional roles in the cell by regulating multiple regulatory signals that ensure adequate temporal and spatial responses to cellular stress. p53 is usually kept inactive due to ubiquitination by a number of E3 ubiquitin ligases that target p53 for proteasomal degradation. The ubiquitously expressed proto-oncogene Mdm2 is the major E3 ubiquitin ligase involved in this process and is critical for regulating p53 homeostasis. Ubiquitination by E3 ligases may induce cellular relocation of p53 and determine the outcome of p53-mediated stress response, including cell proliferation, apoptosis and efficacy of cancer therapy. In addition to marking p53 for proteasomal degradation, ubiquitination acts as a signal for the degradation-independent functions of p53, such as nuclear export and transcriptional activation. Importantly, the reversible nature of the ubiquitination process and the identification of de-ubiquitination enzymes acting on p53 have added yet another layer of regulatory mechanism controlling p53 activity. This review highlights our current understanding of the mechanisms underlying p53 degradation as well as the significance of the p53 pathway in response to genotoxic stress.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinica Chimica Acta - Volume 438, 1 January 2015, Pages 139-147
نویسندگان
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