description
In humans and other mammals the NOTCH gene family has four members, NOTCH1, NOTCH2, NOTCH3 and NOTCH4, encoded on four different chromosomes. Their transcription is developmentally regulated and tissue specific, but very little information exists on molecular mechanisms of transcriptional regulation. Translation of NOTCH mRNAs is negatively regulated by a number of recently discovered microRNAs (Li et al. 2009, Pang et al.2010, Ji et al. 2009, Kong et al. 2010, Marcet et al. 2011, Ghisi et al. 2011, Song et al. 2009, Hashimoto et al. 2010, Costa et al. 2009). The nascent forms of NOTCH precursors, Pre-NOTCH1, Pre-NOTCH2, Pre-NOTCH3 and Pre-NOTCH4, undergo extensive posttranslational modifications in the endoplasmic reticulum and Golgi apparatus to become functional. In the endoplasmic reticulum, conserved serine and threonine residues in the EGF repeats of NOTCH extracellular domain are fucosylated and glucosylated by POFUT1 and POGLUT1, respectively (Yao et al. 2011, Stahl et al. 2008, Wang et al. 2001, Shao et al. 2003, Acar et al. 2008, Fernandez Valdivia et al. 2011). In the Golgi apparatus, fucose groups attached to NOTCH EGF repeats can be elongated by additional glycosylation steps initiated by fringe enzymes (Bruckner et al. 2000, Moloney et al. 2000, Cohen et al. 1997, Johnston et al. 1997, Chen et al. 2001). Fringe-mediated modification modulates NOTCH signaling but is not an obligatory step in Pre-NOTCH processing. Typically, processing of Pre-NOTCH in the Golgi involves cleavage by FURIN convertase (Blaumueller et al. 1997, Logeat et al. 1998, Gordon et al. 2009, Rand et al. 2000, Chan et al. 1998). The cleavage of NOTCH results in formation of mature NOTCH heterodimers that consist of NOTCH extracellular domain (NEC i.e. NECD) and NOTCH transmembrane and intracellular domain (NTM i.e. NTMICD). NOTCH heterodimers translocate to the cell surface where they function in cell to cell signaling

external resources
NCBI:1269531
REACTOME:R-HSA-1912422
PUBMED:21490058
PUBMED:20805998
PUBMED:21464368
PUBMED:9187150
PUBMED:11707585
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PUBMED:11524432
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PUBMED:20495621
PUBMED:10935626
PUBMED:20351093
PUBMED:19701457
PUBMED:21602795
PUBMED:21551231
PUBMED:9653148

genes
ATP2A1 , ATP2A2 , ATP2A3 , CCND1 , CREBBP , E2F1 , E2F3 , EP300 , KAT2A , B4GALT1 , RBPJ , JUN , LFNG , MFNG , MOV10 , NOTCH1 , NOTCH2 , NOTCH3 , NOTCH4 , FURIN , RAB6A , RFNG , SEL1L , ST3GAL4 , ST3GAL3 , TFDP1 , TFDP2 , TP53 , KAT2B , MAML1 , MAMLD1 , ST3GAL6 , TMED2 , SNW1 , TNRC6B , POFUT1 , AGO1 , AGO2 , TNRC6A , MAML3 , POGLUT1 , TNRC6C , MAML2 , AGO3 , AGO4 , MIR1825 , MIR1281 ,