NCOR:HDAC:TBL1 CSL NCOR corepressor complex NICD1:RBPJ:SNW1 NICD1 displaces co-repressor complex from RBPJ (CSL) Authored: Egan, SE, Orlic-Milacic, M, 2011-11-14 Edited: D'Eustachio, P, 2012-02-06 Edited: Orlic-Milacic, M, 2012-02-10 In the absence of NICD1, RBPJ (CSL) is bound to a co-repressor complex that includes NCOR proteins, NCOR1 and/or NCOR2 (also known as SMRT) and HDAC histone deacetylases. Both NCOR and HDAC proteins interact with RBPJ (CSL) through a repression domain in RBPJ. When bound to the co-repressor complex, RBPJ (CSL) represses transcription of NOTCH target genes (Kao et al. 1998). The co-repressor complex also contains SNW1 (SKIP), which interacts with RBPJ (CSL) in a repression-domain independent way (Zhou et al. 2000), TBL1X (TBL1) and TBL1XR1 (TBLR1) (Perissi et al. 2004). NICD1 binds to RBPJ (CSL) and SNW1 (SKIP) and displaces NCOR and HDAC proteins (Kao et al. 1998). TBL1X and TBL1XR1 facilitate displacement of NCOR and HDAC and positively regulated NOTCH-mediated transcription probably by recruiting the ubiquitin/19S proteasome complex that degrades transcriptional repressors (Perissi et al. 2004, Perissi et al. 2008). SNW1 facilitates NICD1 interaction with RBPJ and NOTCH-mediated transcription (Zhou et al. 2000). It is possible that the co-repressor complex contains additional proteins not described here. Loss-of-function mutations in RBPJ typically result in phenotypes associated with reduced NOTCH function, suggesting that RBPJ activation complex (i.e. NOTCH coactivator complex) is more important than RBPJ repressor complex in control of normal development and homeostasis (Oka et al. 1995). Pubmed10713164 Pubmed14980219 Pubmed18374649 Pubmed7588063 Pubmed9694793 Reactome Database ID Release 431912388 Reactome, http://www.reactome.org ReactomeREACT_118848 Reviewed: Haw, R, 2012-02-06