Reactome | Formation of CSL-NICD coactivator complex

Formation of CSL-NICD coactivator complex

Stable Identifier

R-HSA-212356

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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Formation of CSL-NICD coactivator complex

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Mammalian CSL Coactivator Complexes: Upon activation of Notch signaling, cleavage of the transmembrane Notch receptor releases the Notch Intracellular Domain (NICD), which translocates to the nucleus, where it binds to CSL and displaces the corepressor complex from CSL (reviewed in Mumm, 2000 and Kovall, 2007). The resulting CSL-NICD "binary complex" then recruits an additional coactivator, Mastermind (Mam), to form a ternary complex. The ternary complex then recruits additional, more general coactivators, such as CREB Binding Protein (CBP), or the related p300 coactivator, and a number of Histone Acetytransferase (HAT) proteins, including GCN5 and PCAF (Fryer, 2002). There is evidence that Mam also can subsequently recruit specific kinases that phosphorylate NICD, to downregulate its function and turn off Notch signaling (Fryer, 2004).

Literature References

PubMed ID	Title	Journal	Year
17157496	Structures of CSL, Notch and Mastermind proteins: piecing together an active transcription complex Kovall, RA	Curr Opin Struct Biol	2007
11112321	Notch signaling: from the outside in Kopan, R, Mumm, JS	Dev Biol	2000
15546612	Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover Fryer, CJ, Jones, KA, White, JB	Mol Cell	2004
12050117	Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex Fryer, CJ, Lamar, E, Jones, KA, Kintner, C, Turbachova, I	Genes Dev	2002