Identification and Expression of a Novel Family of bHLH cDNAs Related to Drosophila Hairy and Enhancer of Split

Kokubo, Hiroki; Lun, Yi; Johnson, Randy L.

doi:10.1006/bbrc.1999.0880

Cited by 130 publications

(122 citation statements)

References 41 publications

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“…These genes code for transcriptional repressors of the ''basic helix-loop-helix'' (bHLH) type acting as Notch effectors, downregulating expression of other target genes, such as specific tissue transcription factors. A new family of bHLH type transcription repressors, targets of Notch signalling, indicated as HERP, was recently identified (Kokubo et al, 1999;Iso et al, 2001Iso et al, , 2003a. Although very similar, HES and HERP families have been found to use distinct domains and corepressors for their transcription repressor function.…”

Section: Target Genes Of Notch Signallingmentioning

confidence: 99%

Physiology and pathology of notch signalling system

Bianchi

Dotti

Federico

2005

Journal Cellular Physiology

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Notch proteins encode a family of transmembrane receptors that are part of a signalling transduction system known as Notch signalling, an extremely conserved and widely used mechanism regulating programs governing growth, apoptosis and differentiation in metazoans. Notch signalling begins when the Notch receptor binds ligands and ends when the Notch intracellular domain enters the nucleus and activates transcription of target genes. This core pathway is subjected to a wide array of regulatory influences and protein-protein interactions and is correlated with other signalling pathway. This review will sumarize recent findings concerning the physiology and pathology of Notch signalling in vascular development and homeostasis. Moreover, the clinical phenotypes of Notch3 signalling system pathology will be described, with particular regard to CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) for which the most recent pathogenetic hypotheses are reported.

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Section: Target Genes Of Notch Signallingmentioning

confidence: 99%

Physiology and pathology of notch signalling system

Bianchi

Dotti

Federico

2005

Journal Cellular Physiology

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“…Hairy-related transcription factor (HRT) genes, which are variably named Hey (Leimeister et al, 1999), Hrt (Nakagawa et al, 1999), HERP (Iso et al, 2001a,b), Hesr (Kokubo et al, 1999), CHF (Chin et al, 2000), or gridlock (Zhong et al, 2000), encode a recently identified subfamily of basic helix-loop-helix (bHLH) transcription factors related to the hairy and Enhancer-of-split (HES/E(spl)) proteins (reviewed in Davis and Turner, 2001;Iso et al, 2003). The most remarkable difference that distinguishes HRT from HES is the invariant glycine residue in the basic region that replaces the characteristic proline of HES and the YxxW sequence, followed by a conserved TE(I/V)GAF C-terminal motif that replaces the C-terminal tetrapeptide WRPW motif of HES members.…”

Section: Introductionmentioning

confidence: 99%

Identification of BOIP, a novel cDNA highly expressed during spermatogenesis that encodes a protein interacting with the orange domain of the hairy‐related transcription factor HRT1/Hey1 in Xenopus and mouse

Wayenbergh¹,

Taelman

Pichon³

et al. 2003

Developmental Dynamics

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Hairy-related transcription factor (HRT/Hey) genes encode a novel subfamily of basic helix-loop-helix (bHLH) transcription factors related to the Drosophila hairy and Enhancer-of-split (E(spl)) and the mammalian HES proteins that function as downstream mediators of Notch signaling. Using the yeast two-hybrid approach, a previously uncharacterized protein was identified in Xenopus that interacts with XHRT1 (originally referred to as bc8), one member of the HRT/Hey subclass. This protein is evolutionarily conserved in chordates. It binds to sequences adjacent to the bHLH domain of XHRT1 known as the Orange domain and has been named bc8 Orange interacting protein (BOIP). BOIP shows a rather uniform subcellular localization and is recruited to the nucleus upon binding to XHRT1. In Xenopus, XBOIP mRNA is detected by RNase protection analysis throughout embryogenesis. In the adult, the strongest expression is detected in testis. In the mouse, high levels of BOIP mRNA are also found in adult testis. No expression is detected in the embryo and in any of the other adult organs tested. In situ hybridization revealed that BOIP transcripts were detected almost exclusively in round spermatids and that this expression overlaps with that of Hey1 (HRT1), which is expressed throughout spermatogenesis. In view of the importance of the Orange domain for HRT/Hey function, the newly identified BOIP proteins may serve as regulators specifically of HRT1/Hey1 activity. Developmental Dynamics 228:716 -725, 2003.

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“…These proteins are distantly related to Drosophila Hairy and E(spl) as well as the mammalian homologues (e.g. HES) with the highest sequence identity (ϳ40%) in the bHLH region (1,11,12). Like Hairy/E(spl)/Hes, DEC/STRA/SHARPs contain an orange domain and a proline residue in the DNA binding domain.…”

mentioning

confidence: 99%

DEC1 Negatively Regulates the Expression of DEC2 through Binding to the E-box in the Proximal Promoter

Xie

Song

et al. 2003

Journal of Biological Chemistry

122

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Human DEC (differentially expressed in chondrocytes), mouse STRA (stimulated with retinoic acid), and rat SHARP (split and hairy related protein) proteins constitute a new and structurally distinct class of the basic helix-loop-helix proteins. In each species, two members are identified with a sequence identity of >90% in the basic helix-loop-helix region and ϳ40% in the total proteins, respectively. Recently, we have reported that DEC1 is abundantly expressed in colon carcinomas but not in the adjacent normal tissues. The present study was undertaken to extend the expression study of DEC1 and to determine whether DEC1 and DEC2 had similar expression patterns among paired cancer-normal tissues from the colon, lung, and kidney. Without exceptions, DEC1 was markedly higher in the carcinomas, whereas the opposite was true with DEC2. In stable transfectants, tetracycline-induced expression of DEC1 caused proportional decreases in the expression of DEC2. Co-transfection with DEC1 repressed the activity of a DEC2 promoter reporter by as much as 90%. The repression was observed with wild type DEC1 but not its DNA binding-defective mutants. Studies with deletion and site-directed mutants located, in the proximal promoter, an E-box motif that supported the DEC1-mediated repression. Disruption of this E-box markedly abolished the ability of the reporter to respond to DEC1. Our findings assign for DEC1 the first target gene that is regulated through direct DNA binding. DEC/STRA/ SHARP proteins are highly identical in the DNA binding domain but much more diverse in other areas. DEC1-mediated repression on the expression of DEC2 provides an important mechanism that these transcription factors regulate the cellular function not only by modulating the expression of their target genes but also the expression of members within the same class.The basic helix-loop-helix (bHLH) 1 proteins are intimately associated with developmental events such as cell differentiation and lineage commitment (1-6). The HLH domain in the bHLH motif is responsible for dimerization, whereas the basic region mediates DNA binding (1). Based on sequence alignment and domain analysis, human DEC (differentially expressed in chondrocytes), mouse STRA (stimulated with retinoic acid), and rat SHARP (split and hairy related protein) constitute a new and structurally distinct class of bHLH proteins (7-10). These proteins are distantly related to Drosophila Hairy and E(spl) as well as the mammalian homologues (e.g. HES) with the highest sequence identity (ϳ40%) in the bHLH region (1,11,12). Like Hairy/E(spl)/Hes, DEC/STRA/SHARPs contain an orange domain and a proline residue in the DNA binding domain. However, the proline is located 2 residues more toward the NH 2 terminus (1, 8). Another major structural difference on the functional domains is that DEC/STRA/ SHARPs, unlike Hairy/E(Spl)/Hes proteins, lack the COOHterminal WRPW tetrapeptide motif (13). Through this sequence, Hairy/E(spl)/Hes recruit corepressor Groucho to the transcription regulatory complex (13)....

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Identification and Expression of a Novel Family of bHLH cDNAs Related to Drosophila Hairy and Enhancer of Split

Cited by 130 publications

References 41 publications

Physiology and pathology of notch signalling system

Physiology and pathology of notch signalling system

Identification of BOIP, a novel cDNA highly expressed during spermatogenesis that encodes a protein interacting with the orange domain of the hairy‐related transcription factor HRT1/Hey1 in Xenopus and mouse

DEC1 Negatively Regulates the Expression of DEC2 through Binding to the E-box in the Proximal Promoter

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