Notch signaling pathway (WP1148)

Canis familiaris

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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: [http://www.genome.jp/kegg-bin/show_pathway?org_name=map&mapno=04330&show_description=show KEGG] Adapted from KEGG: http://www.genome.jp/kegg-bin/show_pathway?org_name=cfa&mapno=04330

Authors

Thomas Kelder , Daniela Digles , and Eric Weitz

Activity

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Organisms

Canis familiaris

Communities

Annotations

Pathway Ontology

Notch signaling pathway

Participants

Label Type Compact URI Comment
RBPSUHL GeneProduct ensembl:ENSCAFG00000009670
Q6JDK9_CANFA GeneProduct ensembl:ENSCAFG00000004049
CTBP1 GeneProduct ensembl:ENSCAFG00000016687
CTBP2 GeneProduct ensembl:ENSCAFG00000012775
CREBBP GeneProduct ensembl:ENSCAFG00000019251
KAT2A GeneProduct ensembl:ENSCAFG00000015692
KAT2B GeneProduct ensembl:ENSCAFG00000005810
DLL1 GeneProduct ensembl:ENSCAFG00000004094
DLL3 GeneProduct ncbigene:484508
DLL4 GeneProduct ensembl:ENSCAFG00000009401
JAG1 GeneProduct ensembl:ENSCAFG00000005627
JAG2 GeneProduct ensembl:ENSCAFG00000018401
LFNG GeneProduct ensembl:ENSCAFG00000016399
MFNG GeneProduct ensembl:ENSCAFG00000001503
RFNG GeneProduct ensembl:ENSCAFG00000005933
NOTCH2 GeneProduct ensembl:ENSCAFG00000010476
NOTCH3 GeneProduct ensembl:ENSCAFG00000016107
NOTCH4 GeneProduct ensembl:ENSCAFG00000000791
Q56JJ1_CANFA GeneProduct ensembl:ENSCAFG00000003383
APH1A GeneProduct ensembl:ENSCAFG00000011777
APH1B GeneProduct ensembl:ENSCAFG00000016986
TNFA_CANFA GeneProduct ensembl:ENSCAFG00000000517
PSN1_CANFA GeneProduct ensembl:ENSCAFG00000016815
PSEN2 GeneProduct ensembl:ENSCAFG00000016039
NCSTN GeneProduct ensembl:ENSCAFG00000012557
DVL1 GeneProduct ncbigene:489593
DVL2 GeneProduct ensembl:ENSCAFG00000016066
DVL3 GeneProduct ensembl:ENSCAFG00000012180
NUMB GeneProduct ensembl:ENSCAFG00000016834
NUMBL GeneProduct ensembl:ENSCAFG00000005123
DTX1 GeneProduct ensembl:ENSCAFG00000008951
DTX2 GeneProduct ensembl:ENSCAFG00000013614
DTX3 GeneProduct ensembl:ENSCAFG00000023380
DTX4 GeneProduct ensembl:ENSCAFG00000007651
DTX3L GeneProduct ensembl:ENSCAFG00000011948
RBPJ GeneProduct ncbigene:479122 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. 
 
MAML1 GeneProduct ensembl:ENSCAFG00000000350
NCOR2 GeneProduct ensembl:ENSCAFG00000006985
HES5 GeneProduct ensembl:ENSCAFG00000019421
NOTCH1 GeneProduct ensembl:ENSCAFG00000019633
MAML3 GeneProduct ensembl:ENSCAFG00000003700
HDAC1 GeneProduct ensembl:ENSCAFG00000010597
KCNJ5 GeneProduct ncbigene:489284
SKIP GeneProduct ensembl:ENSCAFG00000019181

References

  1. The ins and outs of notch signaling. Weinmaster G. Mol Cell Neurosci. 1997;9(2):91–102. PubMed Europe PMC Scholia