Notch signaling pathway (Drosophila melanogaster)

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1gene expressionDNAg-secretasecomplexMAPK signaling pathwayS2Ras/Mapco-repressor complexS3NICDNotch Intracellular Domainnotch2NCSTNkat2bkat2azgc:194800TNFHDAC2zgc:66440DVL1CREBBPJAG2numbPTCRALOC568641numblpsen1LOC100148345ADAM17hdac1DVL3DLL3JAG1B8A4R6_DANREctbp2dvl2DLL1DTX4SKIPwu:fc10f03HES5aph1bmfngncor2lfngpsen2B8JI71_DANRELOC100148437APH1ALOC571888MAML1rfngNOTCH1her6zgc:136929dll4rbpjb


Description

The Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch proteins (Notch1-Notch4 in vertebrates) are single-pass receptors that are activated by the Delta (or Delta-like) and Jagged/Serrate families of membrane-bound ligands. They are transported to the plasma membrane as cleaved, but otherwise intact polypeptides. Interaction with ligand leads to two additional proteolytic cleavages that liberate the Notch intracellular domain (NICD) from the plasma membrane. The NICD translocates to the nucleus, where it forms a complex with the DNA binding protein CSL, displacing a histone deacetylase (HDAc)-co-repressor (CoR) complex from CSL. Components of an activation complex, such as MAML1 and histone acetyltransferases (HATs), are recruited to the NICD-CSL complex, leading to the transcriptional activation of Notch target genes.

Source: KEGG

Adapted from KEGG: http://www.genome.jp/kegg-bin/show_pathway?org_name=dre&mapno=04330

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP268(r29891) with a 65% conversion rate.

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Ontology Terms

 

Bibliography

  1. Weinmaster G; ''The ins and outs of notch signaling.''; Mol Cell Neurosci, 1997 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
116928view09:46, 16 May 2021EweitzModified title
111052view14:43, 3 July 2020L DupuisConnected line
110031view18:29, 13 April 2020Khanspersupdated interactions, replaced lines with graphics
109432view09:57, 17 March 2020L DupuisConverted interaction to graphical line (where applicable)
109399view16:27, 16 March 2020L DupuisConverted interactions to graphical lines
97076view18:28, 26 April 2018TeacupConnected lines
79442view06:36, 22 March 2015EgonwUpdated the 'Uniprot-TrEMBL' data source spelling.
79347view17:10, 21 March 2015Khanspersupdate
79346view17:09, 21 March 2015KhanspersReverted to version '11:20, 26 June 2013' by Khanspers
68724view21:58, 6 July 2013MaintBotUpdated to 2013 gpml schema
67523view11:20, 26 June 2013DdiglesOntology Term : 'Notch signaling pathway' added !
62826view04:33, 3 May 2013MaintBotUpdated UniProt data source
40899view22:35, 1 March 2011MaintBotRemoved redundant pathway information and comments
35615view16:01, 12 February 2010Thomasadded literature
35614view16:00, 12 February 2010ThomasModified description
21117view11:30, 14 November 2008MaintBot[[Pathway:Drosophila melanogaster:Notch Signaling Pathway KEGG]] moved to [[Pathway:WP208]]: Moved to stable identifier
8519view14:01, 7 January 2008MaintBotAdded to category $category
8517view14:01, 7 January 2008A.J.CaroloUploaded new pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADAM17GeneProduct
APH1AGeneProduct
B8A4R6_DANREGeneProductENSDARG00000079552 (Ensembl)
B8JI71_DANREGeneProductENSDARG00000079519 (Ensembl)
CREBBPGeneProduct
DLL1GeneProduct
DLL3GeneProduct
DTX4GeneProduct
DVL1GeneProduct
DVL3GeneProduct80972 (Entrez Gene)
HDAC2GeneProduct
HES5GeneProduct359836 (Entrez Gene)
JAG1GeneProduct
JAG2GeneProduct140422 (Entrez Gene)
LOC100148345GeneProductENSDARG00000062840 (Ensembl)
LOC100148437GeneProductENSDARG00000075504 (Ensembl)
LOC568641GeneProductENSDARG00000074148 (Ensembl)
LOC571888GeneProduct571888 (Entrez Gene)
MAML1GeneProductENSDARG00000076466 (Ensembl)
NCSTNGeneProductENSDARG00000073668 (Ensembl)
NOTCH1GeneProduct
PTCRAGeneProduct
SKIPGeneProduct
TNFGeneProduct
aph1bGeneProductENSDARG00000005612 (Ensembl)
ctbp2GeneProductENSDARG00000044062 (Ensembl)
dll4GeneProductENSDARG00000070425 (Ensembl)
dvl2GeneProductENSDARG00000056184 (Ensembl)
hdac1GeneProductENSDARG00000015427 (Ensembl)
her6GeneProductENSDARG00000006514 (Ensembl)
kat2aGeneProductENSDARG00000006017 (Ensembl)
kat2bGeneProductENSDARG00000062634 (Ensembl)
lfngGeneProductENSDARG00000037879 (Ensembl)
mfngGeneProductENSDARG00000042925 (Ensembl)
ncor2GeneProductENSDARG00000000966 (Ensembl)
notch2GeneProductENSDARG00000043130 (Ensembl)
numbGeneProductENSDARG00000027279 (Ensembl)
numblGeneProductENSDARG00000024043 (Ensembl)
psen1GeneProductENSDARG00000004870 (Ensembl)
psen2GeneProductENSDARG00000015540 (Ensembl)
rbpjbGeneProduct563306 (Entrez Gene) aka RBP-Jkappa aka CBF1. Serves as a co-factor for the processed notch receptor after translocation to the nucleus to activate down-stream notch transcription. PMID: 15187023. In the nucleus, NIC (processed notch) regulates transcription through association with the DNA-binding protein RBP-J (also known as CBF1, KBF2, or CSL). The primary gene targets of RBP-J include members of the hairy and enhancer of split (HES) and hairy related transcription factor (HRT) families of basic-helix-loop-helix transcriptional repressors. In the absence of NIC, RBP-J actively represses transcription by way of recruitment of a corepressor complex.8 Nuclear translocation of NIC leads to dissociation of repressor proteins from RBP-J and formation of a coactivator complex.9-13. PMID: 15194757. RBP-J is a downstream target of the Notch pathway, a conserved signal transduction pathway that is important in development and cell fate determination (43). The intracellular domain (ICD) of activated Notch is released from the membrane through proteolytic cleavage and is translocated to the nucleus, where it is directed to target promoters through interaction with RBP-J (47, 68). RBP-J is a repressor in the ground state; its interaction with Notch ICD relieves this repression and turns on target genes. Interestingly, KSHV is not the only virus that has parasitized this pathway. Several viral transcription factors, e.g., EBNA2 and EBNA3 of Epstein-Barr virus and the 13S isoform of adenovirus E1A, are known to bind and activate target genes via RBP-J interactions (1, 22, 25, 26, 29). In all cases, the viral proteins target the same (central repressive) domain of RBP-J that is targeted by Notch, although KSHV RTA is capable of interactions with an additional region of RBP-J in vitro (33). RBP-J can bind RTA and recruit it to its cognate recognition site; when this happens, the activation function of RTA can relieve RBP-J-mediated repression and upregulate expression of the targeted gene. EMSA studies reveal that both sites A and C can bind to RBP-J; sequence inspection reveals that site A is a novel functional variant of known RBP-J recognition sites. 



rfngGeneProductENSDARG00000019746 (Ensembl)
wu:fc10f03GeneProductENSDARG00000052139 (Ensembl)
zgc:136929GeneProductENSDARG00000019213 (Ensembl)
zgc:194800GeneProductENSDARG00000032933 (Ensembl)
zgc:66440GeneProductENSDARG00000025766 (Ensembl)

Annotated Interactions

No annotated interactions
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