RGD Reference Report - HERP1 is a cell type-specific primary target of Notch. - Rat Genome Database

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HERP1 is a cell type-specific primary target of Notch.

Authors: Iso, T  Chung, G  Hamamori, Y  Kedes, L 
Citation: Iso T, etal., J Biol Chem 2002 Feb 22;277(8):6598-607.
RGD ID: 70528
Pubmed: PMID:11741889   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M110495200   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hey1RatNotch signaling pathway  IDA  RGD 
Hey2RatNotch signaling pathway  IDA  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HEY2HumanNotch signaling pathway   ISOHey2 (Rattus norvegicus) RGD 
Hey1RatNotch signaling pathway   IDA  RGD 
Hey2RatNotch signaling pathway   IDA  RGD 
Hey2MouseNotch signaling pathway   ISOHey2 (Rattus norvegicus) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Hey1  (hes-related family bHLH transcription factor with YRPW motif 1)
Hey2  (hes-related family bHLH transcription factor with YRPW motif 2)

Genes (Mus musculus)
Hey2  (hairy/enhancer-of-split related with YRPW motif 2)

Genes (Homo sapiens)
HEY2  (hes related family bHLH transcription factor with YRPW motif 2)

Objects referenced in this article
Gene Hey1 hairy/enhancer-of-split related with YRPW motif 1 Mus musculus
Gene Rbpj recombination signal binding protein for immunoglobulin kappa J region Mus musculus

Additional Information