Research article summary (published 27 Apr 2004):

Identification of two binding regions for the suppressor of hairless protein within the intracellular domain of Drosophila notch.

Full Abstract

Notch is a phylogenetically conserved transmembrane receptor that is required for many aspects of animal development. Upon ligand stimulation, a fragment of Notch is released proteolytically and enters the nucleus to form a complex with the DNA-binding protein CSL (CBF1/Suppressor of Hairless/Lag1) and activate transcription of Notch-CSL target genes. The physical structure of the Notch-CSL complex remains unclear, however, clouding the interpretation of previous efforts to correlate Notch structure and function. We have, therefore, characterized the binding of Drosophila CSL (called Suppressor of Hairless, or Su(H)) to the intracellular domain of Drosophila Notch both in vitro and in vivo. We report the identification of two Su(H) binding regions in Notch. The first is in the juxtamembrane region (the "RAM" domain). The second is just C-terminal to the Notch ankyrin repeats, overlapping or identical to two previously proposed nuclear localization sequences, in a domain we term PPD (potential phosphorylated domain). The ankyrin repeats themselves do not bind to Su(H); however, they substantially enhance binding of Su(H) to the more C-terminal region. Consistent with this picture, removal of either the Ram or PPD binding sites, separately, modestly reduces Notch activity in vivo, whereas removal of both renders Notch severely defective. These results clarify the relationship between Notch and CSL, help to explain the importance of the ankyrin repeats in Notch signaling, and reconcile many apparently contradictory results from previous Notch structure/function studies. Moreover, they suggest a second function for the Notch nuclear localization sequence elements.

Author information

Author/s: Le Gall, Maude (M); Giniger, Edward (E);

Affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.

Grants: GM 57830 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Journal: The Journal of biological chemistry (J Biol Chem), published in United States. (Language: eng)

Reference: 2004-Jul; vol 279 (issue 28) : pp 29418-26

Dates: Created 2004/07/05; Completed 2004/08/24; Revised 2007/11/14;

PMID: 15123610, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Amino Acid Sequence Animals Animals, Genetically Modified Binding Sites Drosophila Proteins - genetics; metabolism Drosophila melanogaster - embryology; physiology Humans Membrane Proteins - chemistry; genetics; metabolism Molecular Sequence Data

Mutagenesis, Site-Directed Peptide Fragments - chemistry; genetics; metabolism Protein Binding Protein Structure, Tertiary Receptors, Notch Recombinant Fusion Proteins - genetics; metabolism Repetitive Sequences, Nucleic Acid Repressor Proteins - genetics; metabolism Sequence Alignment

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Drosophila Proteins (0) ; Membrane Proteins (0) ; Peptide Fragments (0) ; Receptors, Notch (0) ; Recombinant Fusion Proteins (0) ; Repressor Proteins (0) ; notch protein, Drosophila (0) ; suppressor of Hairless protein, Drosophila (0)

Related articles

These are the most related articles currently in our database:

• Distinct and collaborative roles of Drosophila EXT family proteins in morphogen signalling and gradient formation. Mar 2004
• Hedgehog lipid modifications are required for Hedgehog stabilization in the extracellular matrix. 3 Jan 2006
• Drosophila RNA binding proteins. 30 Dec 2005
• Huntingtin interacting protein 1 can regulate neurogenesis in Drosophila. 30 Jul 2008
• The Drosophila muscle LIM protein, Mlp84B, cooperates with D-titin to maintain muscle structural integrity. 27 May 2007
• neuralized Encodes a peripheral membrane protein involved in delta signaling and endocytosis. 29 Nov 2001
• Regulatory mechanisms required for DE-cadherin function in cell migration and other types of adhesion. 27 Aug 2005
• The Drosophila pho-like gene encodes a YY1-related DNA binding protein that is redundant with pleiohomeotic in homeotic gene silencing. 30 Dec 2002
• Differential expression of the Drosophila BX-C in polytene chromosomes in cells of larval fat bodies: a cytological approach to identifying in vivo targets of the homeotic Ubx, Abd-A and Abd-B proteins. 30 Jul 2003
• Groucho-dependent repression by sloppy-paired 1 differentially positions anterior pair-rule stripes in the Drosophila embryo. 13 Dec 2004

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a larger map of 100+ related articles.