کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5525606 1401494 2016 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ArticlepVHL mediates K63-linked ubiquitination of IKKβ, leading to IKKβ inactivation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Original ArticlepVHL mediates K63-linked ubiquitination of IKKβ, leading to IKKβ inactivation
چکیده انگلیسی


- pVHL mediates K63-ubiquitination of IKKβ, which inhibits IKKβ phosphorylation.
- Prolyl hydroxylase activity is required for K63-ubiquitination of IKKβ.
- The data disclose a new insight into the mechanism of NF-kB activation by hypoxia.

Nuclear factor (NF)-κB is a transcription factor that plays an important role in many biological functions. Regulation of NF-κB activity is complicated, and ubiquitination is essential for NF-κB activation. Hypoxia can activate NF-κB. However, the underlying mechanism remains unclear. pVHL is a tumour suppressor and functions as an adaptor of E3-ligase. In this study, we demonstrated that pVHL inhibits NF-κB by mediating K63-ubiquitination of IKKβ, which is dependent on oxygen. We found that pVHL mediates K63-linked ubiquitination of IKKβ, which is an upstream regulator of NF-κB. The pVHL-mediated K63-ubiquitination of IKKβ prevents TAK1 binding, which leads to the inhibition of IKKβ phosphorylation and NF-κB activation. pVHL-mediated K63-ubiquitination of IKKβ is inhibited under hypoxia. DMOG, which is a specific inhibitor of prolyl hydroxylases, also suppresses K63-ubiquitination of IKKβ. Prolyl hydroxylase (PHD) 1 enhances K63-ubiquitination of IKKβ and inhibits IKKβ phosphorylation. These results suggest a novel function for pVHL in mediating K63-linked ubiquitination of IKKβ, which plays a role in the regulation of IKK/NF-κB signalling. The results also provide new insight into the mechanism of NF-κB activation through hypoxia.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 383, Issue 1, 1 December 2016, Pages 1-8
نویسندگان
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