NICD1 displaces co-repressor complex from RBPJ (CSL)

Stable Identifier
R-HSA-1912388
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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).

Literature References
PubMed ID Title Journal Year
10713164 SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function

Zhou, S, Fujimuro, M, Hsieh, JJ, Chen, L, Miyamoto, A, Weinmaster, G, Hayward, SD

Mol Cell Biol 2000
14980219 A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors

Perissi, V, Aggarwal, A, Glass, CK, Rose, DW, Rosenfeld, MG

Cell 2004
9694793 A histone deacetylase corepressor complex regulates the Notch signal transduction pathway

Kao, HY, Ordentlich, P, Koyano-Nakagawa, N, Tang, Z, Downes, M, Kintner, CR, Evans, RM, Kadesch, T

Genes Dev 1998
7588063 Disruption of the mouse RBP-J kappa gene results in early embryonic death

Oka, C, Nakano, T, Wakeham, A, de la Pompa, JL, Mori, C, Sakai, T, Okazaki, S, Kawaichi, M, Shiota, K, Mak, TW, Honjo, T

Development 1995
18374649 TBL1 and TBLR1 phosphorylation on regulated gene promoters overcomes dual CtBP and NCoR/SMRT transcriptional repression checkpoints

Perissi, V, Scafoglio, C, Zhang, J, Ohgi, KA, Rose, DW, Glass, CK, Rosenfeld, MG

Mol Cell 2008
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