HES1 and cholangiocarcinoma: Ishimura and colleagues [127] showed that in mouse CCA cell lines, NO is able to induce the cleavage of the NICD1, which translocates into the nucleus to form a transcriptional complex with recombination signal-binding protein 1 for J-kappa (RBPj), up-regulating several target genes, among which hairy and enhancer of split-1 (Hes-1).