c-Rel (NF-kB subunit), HDAC2, NOTCH1 receptor, SKIP (Ski-interacting protein), PCAF, MAML1, Cullin 1, NOTCH1 receptor = NOTCH1 (NEXT), NOTCH1 precursor, p63, NOTCH1 receptor = NOTCH1 (NEXT), TLE, None, ADAM17, SAP30, FBXW7, Manic fringe glycosyltransferase, DLL4, HES1, gamma-Secretase complex, GCN5, MYOD, p300, NOTCH1 receptor, Histone deacetylase class I, HEY1, Jagged1, NOTCH1 (NEXT), CIR, Histone H4, NFKBIA, NOTCH1 (NICD), SMRT, N-CoR, Histone H3, Radical fringe, Jagged2, p73, HEY2, RBP-J kappa (CBF1), Lunatic fringe, Furin, DLL1, None, HDAC1
Notch Signaling Pathway
Notch homolog 1 translocation-associated ( NOTCH1 ) is synthesized as NOTCH1 precursor, which is cleaved by Furin to NOTCH1 receptor form. NOTCH1 receptor is activated by Jagged . O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase ( fringe )-dependent glycosylation of NOTCH1 receptor increases its ability to bind Delta-like ( DLL ) , but prevents NOTCH1 receptor activation by Jagged. After activation NOTCH1 receptor is cleaved by Presenilin 1 and ADAM metallopeptidase domain 17 ( ADAM17 ). Intracellular domain of NOTCH1 ( NOTCH1 (NICD) ) is transported to nucleus and participates in Recombination signal binding protein for immunoglobulin kappa J region ( RBP-J kappa (CBF1) )-mediated transcription .
RBP-J kappa (CBF1) can act as transcription repressor or activator dependent on protein complex, which it recruits to DNA , , . RBP-J kappa (CBF1) acts as gene repressor in a complex with co-repressors Nuclear receptor co-repressor 2 ( SMRT )/Nuclear receptor co-repressor 1 ( N-CoR )/ Histone deacetylase 1 ( HDAC1 ) ,  or CBF1 interacting corepressor ( CIR )/ Sin3A-associated protein 30kDa ( SAP30 )/ Histone deacetylase 2 ( HDAC2 ) , . HDAC participates in histone deacetylation, which prevents transcription. SMRT and CIR function as linkers between HDAC and RBP-J kappa (CBF1) via direct binding of linker protein SNW domain containing 1 ( SKIP ) , , , . NOTCH1 (NICD) binding to SKIP competes with SMRT  and, possibly, CIR . NOTCH1 (NICD) recruits Mastermind-like 1 ( MAML1 ), which facilitates E1A binding protein p300 ( p300 ) recruitment. The last one in turn facilitates p300/CBP-associated factor ( PCAF ) recruitment. Complex MAML1/ p300/ PCAF acts as histone acetylase and assist chromatin remodeling. NOTCH1 (NICD) competition with RBP-J kappa (CBF1) corepressors determines positive regulation of transcription by NOTCH1 (NICD).
Notch signaling is shut off by ubiquitin-proteasome-mediated degradation of NOTCH1 (NICD) by F-box and WD repeat domain containing 7 ( FBXW7 ) after a nuclear phosphorylation event .