Since the conversion of the phosphorylation target Serine199 to the nonphosphorylatable alanine had such a drastic effect on the NOTCH1 level, we strongly believe that the phosphorylation of S199, which was most likely mediated by the cAMP-activated kinase (protein kinase A (PKA)), alters the structure of PHF6 in such a way that the phosphorylated PHF6 can function as a tumor suppressor and induce the expression of NOTCH1. This evidence concerns the gene NOTCH1 and neoplasm.