Notch signaling pathway (WP1148)

Canis familiaris

Authors

Thomas Kelder , Daniela Digles , Eric Weitz , and Kristina Hanspers

Activity

last edited

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Cited In

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Organisms

Canis familiaris

Communities

Annotations

Pathway Ontology

Notch signaling pathway

Participants

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

References

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