Phase Separation Mediates NUP98 Fusion Oncoprotein Leukemic Transformation.
Bappaditya ChandraNicole L MichmerhuizenHazheen K ShirnekhiSwarnendu TripathiBrittany J PiosoDavid W BaggettDiana M MitreaIlaria IacobucciMichael R WhiteJingjing ChenCheon-Gil ParkHuiyun WuStanley PoundsAnna MedyukhinaKhaled A KhairyQingsong GaoChunxu QuSherif AbdelhamedScott D GormanSimranjot BawaCarolyn MaslankaSwati KingerPriyanka DograMylene C FerrolinoDanika Di GiacomoCristina MecucciJeffery M KlcoCharles G MullighanRichard W KriwackiPublished in: Cancer discovery (2022)
We show that homotypic and heterotypic mechanisms of LLPS control NUP98-HOXA9 puncta formation, modulating transcriptional activity and transforming hematopoietic cells. Importantly, these mechanisms are generalizable to other NUP98 FOs that share similar domain structures. These findings address long-standing questions on how nuclear puncta form and their link to leukemogenesis. This article is highlighted in the In This Issue feature, p. 873.