Fig. 4

NPM1 is the contextual determinant of NPM1 and HEXIM1 nucleocytoplasmic shuttling. (1) Nucleophosmin (NPM1) binds to HEXIM1 leading to proteasome-mediated degradation of HEXIM1 and resulting in activation of P-TEFb-dependent RNA Pol II transcription. (2) The cytoplasmic mutant of NPM1 (NPM1c+) sequesters HEXIM1, an inhibitor of P-TEFb, in the cytoplasm, thereby resulting in a higher level of RNA Pol II transcription in acute myeloid leukemia (AML)