Among the residues that contribute to this negatively charged surface, we focused our attention on three residues, namely D36, E39 and E93, because they were previously shown to play a role in the interaction of NPM1 with the tumor suppressor p14ARF.29 To establish their involvement in binding Fbw7γ*, these residues were all mutated to alanine, as single or double mutants; a triple mutant was also prepared. Here, NPM1 is linked to neoplasm.