PathwayStep5537 PathwayStep5550 Activated NOTCH1 Transmits Signal to the Nucleus NOTCH1 Intracellular Domain Regulates Transcription Signaling by NOTCH1 Authored: Egan, SE, Orlic-Milacic, M, 2011-11-14 Edited: D'Eustachio, P, 2012-02-06 Edited: Orlic-Milacic, M, 2012-02-10 GENE ONTOLOGYGO:0007219 NOTCH1 functions as both a transmembrane receptor presented on the cell surface and as a transcriptional regulator in the nucleus.<br><br>NOTCH1 receptor presented on the plasma membrane is activated by a membrane bound ligand expressed in trans on the surface of a neighboring cell. In trans, ligand binding triggers proteolytic cleavage of NOTCH1 and results in release of the NOTCH1 intracellular domain, NICD1, into the cytosol.<br><br>NICD1 translocates to the nucleus where it associates with RBPJ (also known as CSL or CBF) and mastermind-like (MAML) proteins (MAML1, MAML2, MAML3 or MAMLD1) to form NOTCH1 coactivator complex. NOTCH1 coactivator complex activates transcription of genes that possess RBPJ binding sites in their promoters. <br><br> Pubmed10206645 Pubmed10713164 Pubmed10879540 Pubmed10882063 Pubmed10964718 Pubmed11006133 Pubmed11044625 Pubmed11226752 Pubmed11461910 Pubmed11585921 Pubmed11740940 Pubmed12050117 Pubmed12354787 Pubmed12391150 Pubmed12530964 Pubmed14567914 Pubmed14980219 Pubmed15107403 Pubmed15546612 Pubmed15574878 Pubmed15652348 Pubmed15824097 Pubmed15965470 Pubmed16256737 Pubmed16284625 Pubmed16530044 Pubmed17003037 Pubmed17028573 Pubmed17114293 Pubmed18043734 Pubmed18077452 Pubmed18094723 Pubmed18237417 Pubmed18296446 Pubmed18374649 Pubmed18628966 Pubmed19524514 Pubmed19567869 Pubmed19726682 Pubmed20418862 Pubmed20972443 Pubmed7566092 Pubmed8001118 Pubmed8313469 Pubmed8649374 Pubmed8687460 Pubmed9244301 Pubmed9315665 Pubmed9462510 Pubmed9590294 Pubmed9620803 Pubmed9694793 Pubmed9819428 Reactome Database ID Release 431980143 Reactome, http://www.reactome.org ReactomeREACT_118859 Reviewed: Haw, R, 2012-02-06