NICD1 displaces NCOR co-repressor complex from CSL

Stable Identifier
Cercopithecus aethiops

Interaction of RBPJ (CSL) with NCOR2 (SMRT) was initially discovered in a yeast two-hybrid assay, using human recombinant proteins, and was confirmed in mammalian cells by co-immunoprecipitation of exogenously expressed human RBPJ and NCOR2 from the mouse fibroblast cell line NIH 3T3, as well as by a mammalian two-hybrid assay. These experiments also established, using a RBPJ repression domain mutant, that the repression domain was necessary for interaction with NCOR2 (Kao et al. 1998). Using a mammalian two-hybrid assay, it was found that RBPJ also interacts with NCOR1 in a repression domain dependent way. Over-expression of NCOR2 inhibits transcriptional activity of TAN-1, a gain-of-function NOTCH1 mutant found in T-ALL, through disrupting the interaction of TAN-1 with RBPJ (Kao et al. 1998). NOTCH target genes were found to be de-repressed when cells were treated with TSA (trichostatin A), an inhibitor of HDAC1. HDAC1, known to interact with NCOR2, was found to interact with RBPJ: exogenously expressed human RBPJ co-immunoprecipitated endogenous mouse HDAC1 from CV-1 cell line, derived by from kidney cells of the vervet monkey (also known as the African green monkey, Cercopithecus aethiops or Chlorobus aethiops). The interaction of HDAC1 with RBPJ was dependent on the presence of repression domain (Kao et al. 1998). The recombinant human protein SNW1 (SKIP) was shown to interact with recombinant human RBPJ as part of a transcriptional repression complex, but stays bound to recombinant mouse NICD1 and RBPJ and aids NOTCH-mediated transcription once the NCOR co-repression complex is displaced by NICD1 (Zhou et al. 2000). Mouse Tbl1x and Tbl1xr1 were also found in the NCOR co-repressor complex (Perissi et al. 2004). Once the NCOR complex is displaced, Tbl1x and Tbl1xr1 remain bound to it and facilitate NICD1-mediated transcription probably by acting as adaptors for recruitment of the ubiquitin conjugating/19S proteasome complex that degrades displaced transcriptional repressors (Perissi et al. 2008, Perissi et al. 2004).

Literature References
PubMed ID Title Journal Year
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Mol Cell Biol 2000
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Perissi, V, Aggarwal, A, Glass, CK, Rose, DW, Rosenfeld, MG

Cell 2004
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Kao, HY, Ordentlich, P, Koyano-Nakagawa, N, Tang, Z, Downes, M, Kintner, CR, Evans, RM, Kadesch, T

Genes Dev 1998
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
Orthologous Events