NOTCH3 coactivator complex, composed of at least NICD3 (NOTCH3 intracellular domain), RBPJ and MAML (MAML1, MAML2 or MAML3; possibly MAMLD1), directly binds to RBPJ elements in the HES1 gene promoter (Lin et al. 2002). STAT1 can bind to STAT response elements in the HES1 gene promoter and enhance HES1 transcription induced by NICD3. In breast cancer, stromal cells secrete RNA-containing exosomes. Upon uptake of exosomes by breast cancer cells, STAT1-dependent antiviral signaling is initiated. Stromal cells also express JAG1 ligand on their surface and, in parallel to STAT1 signaling, activate NOTCH3 signaling in NOTCH3-expressing breast cancer cells. Synergistic activation of NOTCH3 and STAT1 increases breast cancer radiation resistance (Boelens et al. 2014).
Wiemann, BZ, Qiu, Y, Nabet, BY, Ishwaran, H, Wu, TJ, Slingerland, J, Twyman-Saint Victor, C, Xu, B, Minn, AJ, Yoon, T, Ter Brugge, PJ, Jonkers, J, Boelens, MC, Azzam, DJ
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