Document Detail


HERP1 is a cell type-specific primary target of Notch.
MedLine Citation:
PMID:  11741889     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Notch signaling is involved in many cell fate determination events in metazoans. Ligand binding results in proteolytic cleavage to release the signal-transducing Notch intracellular domain (NICD). The nuclear protein RBP-J kappa, when complexed with NICD, acts as a transcriptional activator which, in turn, induces a target gene of Notch such as the repressors HES/E(spl) and HERP2. Under physiological stimulation using co-culture with Notch ligand-expressing cells and target cells expressing Notch receptors, the HES1 gene and the HERP2 gene have been shown to be directly up-regulated by Notch ligand binding. However, expression of another member of the HERP family, HERP1, was not induced by ligand stimulation in any cells tested, leading to the suggestion that HERP1 may not be an immediate target of Notch or that Notch pathways can be cell type-specific. Because HERP1 appears to play a central role in the development of the aorta (Zhong, T. P., Rosenberg, M., Mohideen, M. A., Weinstein, B., and Fishman, M. C. (2000) Science 287, 1820-1824), we re-addressed the issue of its relationship with the Notch pathway by examining its expression in A10 smooth muscle cells derived from thoracic aorta. We show that in these specific cells HERP1 is also a direct target gene of Notch. NICD activates the HERP1 promoter in an RBP-J kappa-dependent manner, and induces expression of endogenous HERP1 mRNA as well as HERP1 protein in A10 cells. Co-culture with Notch ligand-bearing cells induces endogenous HERP1 mRNA expression in A10 cells, and these events occur even in the absence of de novo protein synthesis. In addition, RBP-J kappa proved essential for induction of HERP1 mRNA in Notch signaling because exogenous RBP-J kappa was sufficient to rescue HERP1 mRNA expression in RBP-J kappa-deficient cells. These findings provide the first solid evidence that HERP1 is a novel primary target of Notch and underscores the cell-specific complexity of the Notch regulatory pathway. Given that Notch signaling plays a crucial role in vascular development, Notch may derive its function via HERP family members.
Authors:
Tatsuya Iso; Gene Chung; Yasuo Hamamori; Larry Kedes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2001-12-06
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  277     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-18     Completed Date:  2002-04-24     Revised Date:  2009-08-12    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6598-607     Citation Subset:  IM    
Affiliation:
Institute for Genetic Medicine, Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089-9075, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Aorta
Base Sequence
Basic Helix-Loop-Helix Transcription Factors
Binding Sites
Consensus Sequence
DNA-Binding Proteins / metabolism
Gene Expression Regulation
Genes, Reporter
Genomic Library
Immunoglobulin J Recombination Signal Sequence-Binding Protein
Membrane Proteins / genetics*,  metabolism
Mice
Molecular Sequence Data
Muscle, Smooth, Vascular / metabolism
Nuclear Proteins*
Polymerase Chain Reaction
Promoter Regions, Genetic
Receptors, Notch
Repressor Proteins / genetics*,  metabolism
Sequence Alignment
Sequence Homology, Amino Acid
Sequence Homology, Nucleic Acid
Transcription, Genetic
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/DNA-Binding Proteins; 0/Hairy, HRT1 protein; 0/Immunoglobulin J Recombination Signal Sequence-Binding Protein; 0/Membrane Proteins; 0/Nuclear Proteins; 0/Rbpj protein, mouse; 0/Receptors, Notch; 0/Repressor Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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