NICD1 in complex with RBPJ (CSL) recruits MAML

Stable Identifier
R-HSA-1912394
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

The minimal functional NOTCH coactivator complex that activates transcription from NOTCH regulatory elements is a heterotrimer composed of MAML (mastermind-like), NICD (NOTCH intracellular domain) and RBPJ (CSL) (Fryer et al. 2002). Structural studies indicate that NOTCH:RBPJ complexes can be pre-assembled on promoters of NOTCH-target genes and that MAML binds to a composite groove created by RBPJ and the NOTCH ankyrin domain (Nam et al. 2006). MAML is able to interact directly with a histone acetyltransferases EP300 (p300) and CREBBP. The presence of EP300 strongly activates NOTCH1 coactivator complex-mediated transcription and this positive effect is blocked by Lys-CoA, a selective inhibitor of EP300 histone acetyltransferase activity (Fryer et al. 2002). NICD1:RBPJ:MAML-mediated transcription increases threefold in the presence of both EP300 and PCAF, in comparison with the presence of EP300 alone (Wallberg et al. 2002).

Literature References
PubMed ID Title Journal Year
12391150 p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitro

Wallberg, AE, Pedersen, K, Lendahl, U, Roeder, RG

Mol Cell Biol 2002
12050117 Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex

Fryer, CJ, Lamar, E, Turbachova, I, Kintner, C, Jones, KA

Genes Dev 2002
16530044 Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes

Nam, Y, Sliz, P, Song, L, Aster, JC, Blacklow, SC

Cell 2006
Participants
Participant Of
Orthologous Events
Authored
Reviewed