کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2187635 1096130 2008 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mutational and Energetic Studies of Notch1 Transcription Complexes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Mutational and Energetic Studies of Notch1 Transcription Complexes
چکیده انگلیسی

Notch proteins constitute the receptors of a highly conserved signaling pathway that influences cell fate decisions both during development and in adulthood. A proteolytic cascade induced by ligand stimulation results in release of the intracellular Notch domain from the cell membrane, allowing it to enter the nucleus and form a complex with a DNA-bound transcription factor called CSL (CBF-1/RBP-Jκ, Suppressor of Hairless, and Lag-1) and a coactivator of the Mastermind family. Assembly of this Notch nuclear complex is the key step in the transcriptional response to a Notch signal. In the studies reported here, we mapped residues important for the stabilization of this multiprotein–DNA complex using site-directed mutagenesis, determined the affinity of the three-domain form of CSL for its various partners, and investigated sources of cooperativity in complex formation by monitoring the influence of various components of the complex on the interactions of CSL with its other partners. Our findings are consistent with a model for complex assembly in which the RBP-Jκ-associated molecule domain of Notch increases the effective concentration of the ankyrin domain for its binding site on the Rel-homology region of CSL, enabling docking of the ankyrin domain and subsequent recruitment of the Mastermind-like coactivator.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 376, Issue 1, 8 February 2008, Pages 131–140
نویسندگان
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