PathwayStep5502 PathwayStep5501 PathwayStep5504 PathwayStep5503 PathwayStep5500 PathwayStep5489 PathwayStep5488 PathwayStep5494 PathwayStep5493 PathwayStep5496 PathwayStep5495 PathwayStep5498 PathwayStep5497 PathwayStep5499 PathwayStep5490 PathwayStep5492 PathwayStep5491 MIR181C microRNA binds 3'UTR of NOTCH4 mRNA MIR206 microRNA binds 3'UTR of NOTCH3 mRNA NOTCH1 mRNA translation controlled by miRNAs MIR302A microRNA binds 3'UTR of NOTCH4 mRNA NOTCH3 mRNA translation controlled by miRNAs NOTCH2 mRNA translation controlled by miRNAs NOTCH4 mRNA translation controlled by miRNAs MIR150 microRNA binds 3'UTR of NOTCH3 mRNA NOTCH1 gene transcription p53 positively regulates transcription of MIR34 microRNAs NOTCH4 gene transcription NOTCH3 gene transcription NOTCH2 gene transcription MIR34 microRNAs bind 3'UTR of NOTCH2 mRNA MIR449 microRNAs bind 3'UTR of NOTCH1 mRNA MIR200B/C microRNAs bind NOTCH1 mRNA MIR34 microRNAs bind 3'UTR of NOTCH1 mRNA Pre-NOTCH Transcription and Translation Authored: Egan, SE, Orlic-Milacic, M, 2011-11-14 Edited: D'Eustachio, P, 2012-02-06 Edited: D'Eustachio, P, 2012-05-15 Edited: Gillespie, ME, 2012-02-09 Edited: Jupe, S, 2011-09-27 Edited: May, B, 2012-02-09 Edited: Orlic-Milacic, M, 2012-02-10 In humans, the NOTCH protein family has four members: NOTCH1, NOTCH2, NOTCH3 and NOTCH4. NOTCH1 protein was identified first, as the product of a chromosome 9 gene translocated in T-cell acute lymphoblastic leukemia that was homologous to Drosophila Notch (Ellisen et al. 1991). At the same time, rat Notch1 was cloned (Weinmaster et al. 1991), followed by cloning of mouse Notch1, named Motch (Del Amo et al. 1992). NOTCH2 protein is the product of a gene on chromosome 1 (Larsson et al. 1994). NOTCH2 expression is differentially regulated during B-cell development (Bertrand et al. 2000). NOTCH2 mutations are a rare cause of Alagille syndrome (McDaniell et al. 2006). NOTCH3 is the product of a gene on chromosome 19. NOTCH3 mutations are the underlying cause of CADASIL, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (Joutel et al. 1996). NOTCH4, the last NOTCH protein discovered, is the product of a gene on chromosome 6 (Li et al. 1998). <br><br> MicroRNAs play an important negative role in translation and/or stability of NOTCH mRNAs. MicroRNAs miR-34 (miR-34A, miR-34B and mi-R34C), whose transcription is directly induced by the tumor suppressor protein p53 (Chang et al. 2007, Raver-Shapira et al. 2007, He et al. 2007, Corney et al. 2007) bind and negatively regulate translation of NOTCH1 mRNA (Li et al. 2009, Pang et al. 2010, Ji et al. 2009) and NOTCH2 mRNA (Li et al. 2009). NOTCH1 mRNA translation is also negatively regulated by microRNAs miR-200B and miR-200C (Kong et al. 2010), as well as miR-449A, miR-449B and miR-449C (Marcet et al. 2011). Translation of NOTCH3 mRNA is negatively regulated by microRNAs miR-150 (Ghisi et al. 2011) and miR-206 (Song et al. 2009). Translation of NOTCH4 mRNA is negatively regulated by microRNAs miR-181C (Hashimoto et al. 2010) and miR-302A (Costa et al. 2009). <br><br> Nascent NOTCH peptides are co-translationally targeted to the endoplasmic reticulum for further processing, followed by modification in the Golgi apparatus, before trafficking to the plasma membrane. Endoplasmic reticulum calcium ATPases, positively regulate NOTCH trafficking, possibly by contributing to accurate folding of NOTCH precursors (Periz et al. 1999). Pubmed10545110 Pubmed11187898 Pubmed1425352 Pubmed16773578 Pubmed17540598 Pubmed17540599 Pubmed17554337 Pubmed1764995 Pubmed17823410 Pubmed1831692 Pubmed19714243 Pubmed19723635 Pubmed19773441 Pubmed20080834 Pubmed20351093 Pubmed20495621 Pubmed20805998 Pubmed21551231 Pubmed21602795 Pubmed7698746 Pubmed8878478 Pubmed9693032 Reactome Database ID Release 431912408 Reactome, http://www.reactome.org ReactomeREACT_118568 Reviewed: Haw, R, 2012-02-06 Reviewed: Haw, R, 2012-05-17