کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1950725 1055693 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ubiquitination and phosphorylation in the regulation of NOD2 signaling and NOD2-mediated disease
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Ubiquitination and phosphorylation in the regulation of NOD2 signaling and NOD2-mediated disease
چکیده انگلیسی

The immune system is exquisitely balanced. It has the ability to effectively respond to and control infections while at the same time preventing inappropriate responses to self and environmental antigens. When this response goes awry, either through a failure to activate the immune response, or failure to terminate it, inflammatory pathology results. Posttranslational modifications (PTMs) such as ubiquitination and phosphorylation help ensure that the delicate balance underlying immune signal transduction is maintained. Ubiquitination and phosphorylation affect localization, activity, stability, and interactions of various components of the immune signal transduction machinery. Moreover, ubiquitination and phosphorylation are tightly linked, with one PTM affecting the other. Therefore, in order to find potential therapies for many immune-related pathologies, it is necessary to understand not only how the immune response is activated by ubiquitination and phosphorylation, but also how it is regulated by these PTMs at different stages of the response. An excellent system to study such activation and regulation is the NOD2 pathway. Dysregulation of NOD2 signaling is involved in the pathogenesis of a variety of inflammatory disorders including Crohn's disease, early onset sarcoidosis, and Blau syndrome. More recently NOD2 has been implicated in the development of autoimmune disease, allergy and asthma. This review will focus on what is currently known about how ubiquitination and phosphorylation regulate NOD2 signaling with particular emphasis on novel in vitro substrates which may serve as potential in vivo therapeutic targets for hyperactive NOD2 states. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics.


► The NOD2 pathway is regulated by phosphorylation and ubiquitination.
► A number of disease settings may benefit from inhibition of NOD2 signaling.
► We describe potential therapeutic targets in the NOD2 pathway.
► We describe currently available inhibitors of NOD2 signaling.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1823, Issue 11, November 2012, Pages 2022–2028
نویسندگان
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