MDM4 and melanoma: Importantly, in A375 melanoma, MdmX splicing was shown to sense and transduce the information about the state of the cellular splicing machinery to the p53 pathway, as RNAi-mediated knock-down of individual components of cell splicing machinery was capable of downregulating MdmX expression and inducing wild type p53-dependent transcriptional activity in the absence of DNA damage [10,35].