DELINEATING THE KEY REGIONS AND FUNCTIONS OF NUP98 CONTRIBUTING TO THE LEUKEMOGENIC ACTIVITY OF NUP98-HOX FUSIONS

摘要

To determine the contribution of the common N-terminal truncation of NUP98 in NUP98-translocations resulting in acute myeloid leukemia, we have conducted a structure-function analysis of NUP98 in the context of NUP98-HOXA10HD, a novel, canonical NUP98-Hox fusion that significantly enhances the self-renewal capacity of hematopoietic stem cells and collaborates with Meis1 to induce AML in our mouse models Our results clearly demonstrate that the NUP98 fusion partner does not require interactions with either the nuclear pore complex (NPC) or the Rae1/anaphase promoting complex (APC), but instead, NUP98 seems to function in a transactivation manner by recruitment of CBP/p300 via its FG/GLFG repeats.