As depicted in Figure 3, the final currently known post-transcriptional regulation of Wip1 expression to be discussed is alternative splicing. Alternative splicing of Wip1 was discovered by the cloning of a longer than predicted cDNA fragment of Wip1 that included a region beyond exon 5 that encoded a stop codon (45). Subsequently, two alternatively spliced products were found, one corresponding to the full length protein (PPM1D605) and the second to a shorter version (by 175 base pairs, PPM1D430). The two spliced products share the entire catalytic domain plus an additional 42 residues, suggesting that both proteins have phosphatase activity, which was confirmed by an in vitro phosphatase activity assay with purified recombinant proteins (45). Furthermore, PPM1D605 and PPM1D430 are similarly induced in MCF-7 cells after adriamycin exposure, and both are functional phosphatases, since either the specific knock down of PPM1D430 or the knock-down of both variants resulted in enhanced p53 phosphorylation and stabilization (45). On the other hand, other clues suggest functional differences between the two variants. For example, whereas PPM1D605 expression is ubiquitous, PPM1D430 is highly expressed in the
