کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815916 | 1058525 | 2015 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Disease-associated mutations in IRF6 and RIPK4 dysregulate their signalling functions
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کلمات کلیدی
DBDvWSIADIRF6RIPK4IRFARDBPSCTDPps - PPSAnkyrin repeat domain - آنکرین دامنه را تکرار می کندProtein degradation - تخریب پروتئینmutation - جهشC-terminal domain - دامنه C ترمینالDNA-Binding Domain - دامنه اتصال DNARIPK - ریپکVan der Woude syndrome - سندرم ون دووودCleft lip/palate - شکاف لب / کامinterferon regulatory factor - عامل تنظیمی اینترفرونreceptor-interacting protein kinase - پروتئین کیناز گیرنده گیرنده
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Disease-associated mutations in IRF6 and RIPK4 dysregulate their signalling functions Disease-associated mutations in IRF6 and RIPK4 dysregulate their signalling functions](/preview/png/10815916.png)
چکیده انگلیسی
IRF6 and RIPK4 are critical regulators of keratinocyte differentiation and their mutation cause the developmental syndromes Van der Woude syndrome (VWS) and Bartsocas-Papas syndrome (BPS), respectively. RIPK4 promotes keratinocyte differentiation, in part, by inducing IRF6 transactivator function through the phosphorylation of its C-terminal domain at Ser413 and Ser424. Although more than 200 IRF6 mutations have been identified in VWS, a p.Arg412X nonsense mutation is particularly prevalent. A RIPK4 p.Ser376X nonsense mutation in BPS was also recently identified. Here, we demonstrated for the first time that the truncation of IRF6 at Arg412 causes its rapid proteasome-dependent degradation. The truncation of IRF6 also prevented the induction of its transactivator function by RIPK4. Similarly, the p.Ser376X mutation in RIPK4 impaired its induction of IRF6 transactivator function. The mutation also inhibited the stabilisation of β-catenin by RIPK4, and thus may additionally impair Wnt signalling. Collectively, our findings provide important mechanistic insight into how the p.Arg412X and p.Ser376X mutations may cause VWS and BPS, respectively.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 27, Issue 7, July 2015, Pages 1509-1516
Journal: Cellular Signalling - Volume 27, Issue 7, July 2015, Pages 1509-1516
نویسندگان
Mei Qi Kwa, Jennifer Huynh, Eric C. Reynolds, John A. Hamilton, Glen M. Scholz,