Pre-NOTCH Expression and Processing

Ghisi M, Corradin A, Basso K, Frasson C, Serafin V, Mukherjee S, Mussolin L, Ruggero K, Bonanno L, Guffanti A, De Bellis G, Gerosa G, Stellin G, D'Agostino DM, Basso G, Bronte V, Indraccolo S, Amadori A, Zanovello P. Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150. Blood. 2011 Jun 30;117(26):7053–62. doi: 10.1182/blood-2010-12-326629. PMID: 21551231.; Yao D, Huang Y, Huang X, Wang W, Yan Q, Wei L, Xin W, Gerson S, Stanley P, Lowe JB, Zhou L. Protein O-fucosyltransferase 1 (Pofut1) regulates lymphoid and myeloid homeostasis through modulation of Notch receptor ligand interactions. Blood. 2011 May 26;117(21):5652–62. PMID: 21464368; PMCID: PMC3110024.; Marcet B, Chevalier B, Luxardi G, Coraux C, Zaragosi LE, Cibois M, Robbe-Sermesant K, Jolly T, Cardinaud B, Moreilhon C, Giovannini-Chami L, Nawrocki-Raby B, Birembaut P, Waldmann R, Kodjabachian L, Barbry P. Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway. Nat Cell Biol. 2011 Jun;13(6):693–9. doi: 10.1038/ncb2241. PMID: 21602795.; Fernandez-Valdivia R, Takeuchi H, Samarghandi A, Lopez M, Leonardi J, Haltiwanger RS, Jafar-Nejad H. Regulation of mammalian Notch signaling and embryonic development by the protein O-glucosyltransferase Rumi. Development. 2011 May;138(10):1925–34. PMID: 21490058; PMCID: PMC3082299.; Kong D, Banerjee S, Ahmad A, Li Y, Wang Z, Sethi S, Sarkar FH. Epithelial to Mesenchymal Transition Is Mechanistically Linked with Stem Cell Signatures in Prostate Cancer Cells. PLoS ONE. 2010 Aug 27;5(8):e12445. doi: 10.1371/journal.pone.0012445.; Pang RT, Leung CO, Ye TM, Liu W, Chiu PC, Lam KK, Lee KF, Yeung WS. MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. Carcinogenesis. 2010 Jun;31(6):1037–44. doi: 10.1093/carcin/bgq066. PMID: 20351093.; Hashimoto Y, Akiyama Y, Otsubo T, Shimada S, Yuasa Y. Involvement of epigenetically silenced microRNA-181c in gastric carcinogenesis. Carcinogenesis. 2010 May;31(5):777–84. doi: 10.1093/carcin/bgq013. PMID: 20080834.; Costa FF, Seftor EA, Bischof JM, Kirschmann DA, Strizzi L, Arndt K, Bonaldo Mde F, Soares MB, Hendrix MJ. Epigenetically reprogramming metastatic tumor cells with an embryonic microenvironment. Epigenomics. 2009 Dec;1(2):387–98. PMID: 20495621; PMCID: PMC2872497.; Song G, Zhang Y, Wang L. MicroRNA-206 Targets notch3, Activates Apoptosis, and Inhibits Tumor Cell Migration and Focus Formation. Journal of Biological Chemistry. 2009 Nov;284(46):31921–7. doi: 10.1074/jbc.m109.046862.; Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E, Marcinkiewicz L, Jiang J, Yang Y, Schmittgen TD, Lopes B, Schiff D, Purow B, Abounader R. MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res. 2009 Oct 01;69(19):7569–76. PMID: 19773441; PMCID: PMC2756313.; Ji Q, Hao X, Zhang M, Tang W, Yang M, Li L, Xiang D, DeSano JT, Bommer GT, Fan D, Fearon ER, Lawrence TS, Xu L. MicroRNA miR-34 Inhibits Human Pancreatic Cancer Tumor-Initiating Cells. PLoS ONE. 2009 Aug 28;4(8):e6816. doi: 10.1371/journal.pone.0006816.; Gordon WR, Vardar-Ulu D, L'Heureux S, Ashworth T, Malecki MJ, Sanchez-Irizarry C, McArthur DG, Histen G, Mitchell JL, Aster JC, Blacklow SC. Effects of S1 Cleavage on the Structure, Surface Export, and Signaling Activity of Human Notch1 and Notch2. PLoS ONE. 2009 Aug 24;4(8):e6613. doi: 10.1371/journal.pone.0006613.; Stahl M, Uemura K, Ge C, Shi S, Tashima Y, Stanley P. Roles of Pofut1 and O-Fucose in Mammalian Notch Signaling. Journal of Biological Chemistry. 2008 May;283(20):13638–51. doi: 10.1074/jbc.m802027200.; Acar M, Jafar-Nejad H, Takeuchi H, Rajan A, Ibrani D, Rana NA, Pan H, Haltiwanger RS, Bellen HJ. Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling. Cell. 2008 Jan 25;132(2):247–58. PMID: 18243100; PMCID: PMC2275919.; Shao L, Moloney DJ, Haltiwanger R. Fringe Modifies O-Fucose on Mouse Notch1 at Epidermal Growth Factor-like Repeats within the Ligand-binding Site and the Abruptex Region. Journal of Biological Chemistry. 2003 Mar;278(10):7775–82. doi: 10.1074/jbc.m212221200.; Chen J, Moloney DJ, Stanley P. Fringe modulation of Jagged1-induced Notch signaling requires the action of beta 4galactosyltransferase-1. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13716–21. PMID: 11707585; PMCID: PMC61107.; Wang Y, Shao L, Shi S, Harris RJ, Spellman MW, Stanley P, Haltiwanger RS. Modification of epidermal growth factor-like repeats with O-fucose. Molecular cloning and expression of a novel GDP-fucose protein O-fucosyltransferase. J Biol Chem. 2001 Oct 26;276(43):40338–45. doi: 10.1074/jbc.m107849200. PMID: 11524432.; Moloney DJ, Panin VM, Johnston SH, Chen J, Shao L, Wilson R, Wang Y, Stanley P, Irvine KD, Haltiwanger RS, Vogt TF. Fringe is a glycosyltransferase that modifies Notch. Nature. 2000 Jul 27;406(6794):369–75. doi: 10.1038/35019000. PMID: 10935626.; Brückner K, Perez L, Clausen H, Cohen S. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature. 2000 Jul 27;406(6794):411–5. doi: 10.1038/35019075. PMID: 10935637.; Rand MD, Grimm LM, Artavanis-Tsakonas S, Patriub V, Blacklow SC, Sklar J, Aster JC. Calcium Depletion Dissociates and Activates Heterodimeric Notch Receptors. Molecular and Cellular Biology. 2000 Mar 01;20(5):1825–35. doi: 10.1128/mcb.20.5.1825-1835.2000.; Chan YM, Jan YN. Roles for proteolysis and trafficking in notch maturation and signal transduction. Cell. 1998 Aug 21;94(4):423–6. doi: 10.1016/s0092-8674(00)81583-4. PMID: 9727485.; Logeat F, Bessia C, Brou C, LeBail O, Jarriault S, Seidah NG, Israël A. The Notch1 receptor is cleaved constitutively by a furin-like convertase. Proc. Natl. Acad. Sci. U.S.A. 1998 Jul 07;95(14):8108–12. doi: 10.1073/pnas.95.14.8108.; Blaumueller CM, Qi H, Zagouras P, Artavanis-Tsakonas S. Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane. Cell. 1997 Jul 25;90(2):281–91. doi: 10.1016/s0092-8674(00)80336-0. PMID: 9244302.; Cohen B, Bashirullah A, Dagnino L, Campbell C, Fisher WW, Leow CC, Whiting E, Ryan D, Zinyk D, Boulianne G, Hui CC, Gallie B, Phillips RA, Lipshitz HD, Egan SE. Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila. Nat Genet. 1997 Jul;16(3):283–8. doi: 10.1038/ng0797-283. PMID: 9207795.; Johnston SH, Rauskolb C, Wilson R, Prabhakaran B, Irvine KD, Vogt TF. A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway. Development. 1997 Jun;124(11):2245–54. doi: 10.1242/dev.124.11.2245. PMID: 9187150.

Metabolites



Enzyme

EC Number name full name note
2.3.1.-
2.3.1.286 protein acetyllysine N-acetyltransferase [protein]-N6-acetyl-L-lysine:NAD+ N-acetyltransferase (NAD+-hydrolysing; 2''-O-acetyl-ADP-D-ribose-forming)
2.3.1.48 histone acetyltransferase acetyl-CoA:[protein]-L-lysine acetyltransferase
2.4.1.22 lactose synthase UDP-galactose:D-glucose 4-beta-D-galactosyltransferase
2.4.1.221 peptide-O-fucosyltransferase GDP-beta-L-fucose:protein-(L-serine/L-threonine) O-alpha-L-fucosyltransferase (configuration-inverting)
2.4.1.275 neolactotriaosylceramide beta-1,4-galactosyltransferase UDP-alpha-D-galactose:N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1beta4)-beta-D-glucosyl-(1<->1)-ceramide 4-beta-D-galactosyltransferase
2.4.1.376 EGF-domain serine glucosyltransferase UDP-alpha-D-glucose:[protein with EGF-like domain]-L-serine O-beta-glucosyltransferase (configuration-inverting)
2.4.1.38 beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase UDP-galactose:N-acetyl-beta-D-glucosaminylglycopeptide 4-beta-galactosyltransferase
2.4.1.90 N-acetyllactosamine synthase UDP-galactose:N-acetyl-D-glucosamine 4-beta-D-galactosyltransferase
2.4.2.63 EGF-domain serine xylosyltransferase UDP-alpha-D-xylose:[protein with EGF-like domain]-L-serine O-beta-xylosyltransferase (configuration-inverting)
2.7.11.13 protein kinase C ATP:protein phosphotransferase (diacylglycerol-dependent)
3.4.21.37 leukocyte elastase
3.4.21.75 Furin
3.6.4.13 RNA helicase
3.6.5.2 small monomeric GTPase GTP phosphohydrolase (cell-regulating)


Proteins

Protein ID name full name