کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1936645 1050697 2007 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A Sveinsson’s chorioretinal atrophy-associated missense mutation in mouse Tead1 affects its interaction with the co-factors YAP and TAZ
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
A Sveinsson’s chorioretinal atrophy-associated missense mutation in mouse Tead1 affects its interaction with the co-factors YAP and TAZ
چکیده انگلیسی

Sveinsson’s chorioretinal atrophy (SCRA) is an autosomal dominant eye disease characterized by bilateral chorioretinal degeneration. A missense mutation in the gene encoding the transcription factor TEAD1/TEF-1 (Y421H) is genetically linked to SCRA, but the mechanisms of pathology remain unclear. To study the molecular mechanisms underlying SCRA, a missense mutation corresponding to Y421H in human TEAD1 was introduced into mouse Tead1 (Y410H), and a functional analysis of the mutant protein was performed in RPE-J cells. The missense mutation reduced the ability of Tead1 to interact with the co-factors YAP and TAZ, but not with the co-factors Vgl-1, -2, and -3, in a mammalian two-hybrid assay. A GST pull-down assay showed that the direct interaction between Tead1 and YAP or TAZ was lost owing to the mutation. Amino acid substitutions at position 410 of Tead1 revealed the essentiality of this tyrosine residue to the interaction. The Y410H mutation also abolished the transcriptional activity of Tead1 under the co-expression of YAP or TAZ. These results suggest that SCRA pathogenesis may be due to a loss-of-function of TEAD1 affecting the regulation of its target genes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 361, Issue 4, 5 October 2007, Pages 1022–1026
نویسندگان
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