In the nucleus, NICD3 forms a complex with RBPJ (CBF1, CSL) and MAML (mastermind) proteins MAML1, MAML2 or MAML3 (possibly also MAMLD1). NICD3:RBPJ:MAML complex activates transcription from RBPJ-binding promoter elements (Lin et al. 2002).

Besides NICD3, RBPJ and MAML, NOTCH3 coactivator complex likely includes other proteins shown as components of the NOTCH1 coactivator complex. Since disruption of the RBPJ:NCOR corepressor and MAML-mediated recruitment of transcriptional activators has not been studied in the context of NICD3, it is not shown here. More details are available in the pathway Signaling by NOTCH1.

Many NOTCH-regulated genes have paired RBPJ-binding sites in their promoters, in head-to-head arrangement, and require cooperative formation of dimeric NOTCH transcription complexes for transcriptional activation (Nam et al. 2007).