Physical association of the patient-specific GATA1 mutants with RUNX1 in acute megakaryoblastic leukemia accompanying Down syndrome

Leukemia
Gang XuEtsuro Ito

Abstract

Mutations of the GATA1 gene on chromosome X have been found in almost all cases of transient myeloproliferative disorder and acute megakaryoblastic leukemia (AMKL) accompanying Down syndrome (DS). Although most GATA1 mutations lead to the expression of GATA1s lacking the N-terminal activation domain, we recently found two novel GATA1 proteins with defects in another N-terminal region. It has been suggested that loss of the N-terminal portion of GATA1 might interfere with physiological interactions with the critical megakaryocytic transcription factor RUNX1, and this would imply that GATA1s is not able to interact properly with RUNX1. However, the interaction domain of GATA1 remains controversial. In this study, we show that GATA1 binds to RUNX1 through its zinc-finger domains, and that the C-finger is indispensable for synergy with RUNX1. All of the patient-specific GATA1 mutants interacted efficiently with RUNX1 and retained their ability to act synergistically with RUNX1 on the megakaryocytic GP1balpha promoter, whereas the levels of transcriptional activities were diverse among the mutants. Thus, our data indicate that physical interaction and synergy between GATA1 and RUNX1 are retained in DS-AMKL, although it is still poss...Continue Reading

References

Oct 6, 1997·The EMBO Journal·S DeveauxV Mignotte
Nov 9, 2000·The Journal of Biological Chemistry·R KanezakiE Ito
Jul 3, 2002·Nature Reviews. Cancer·Nancy A Speck, D Gary Gilliland
Aug 13, 2002·Nature Genetics·Joshua WechslerJohn D Crispino
Aug 13, 2002·Nature Genetics·A Thomas Look
Feb 11, 2003·Blood·Kamaleldin E ElagibAdam N Goldfarb
Jul 1, 2004·Molecular and Cellular Biology·David M BarrettGordon D Ginder
Jan 5, 2005·Nature Reviews. Cancer·Johann K Hitzler, Alvin Zipursky
Feb 3, 2005·Molecular and Cellular Biology·Rita FerreiraSjaak Philipsen

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Citations

Oct 16, 2007·Oncogene·A N Goldfarb
Mar 20, 2009·Human Molecular Genetics·Ithamar GanmoreShai Izraeli
Jan 17, 2007·Current Opinion in Pediatrics·Paresh Vyas, John D Crispino
Jul 18, 2012·Molecular and Cellular Biology·Boet van RielFrank Grosveld
Sep 11, 2008·Blood·Kamaleldin E ElagibAdam N Goldfarb
Dec 29, 2011·Frontiers in Bioscience (Landmark Edition)·Kentson Lam, Dong-Er Zhang
Aug 13, 2013·Blood Cells, Molecules & Diseases·Irene RobertsParesh Vyas
Mar 17, 2012·Seminars in Fetal & Neonatal Medicine·Anindita RoyParesh Vyas
Aug 27, 2014·British Journal of Haematology·Irene Roberts, Shai Izraeli
Nov 27, 2019·IUBMB Life·Catherine GarnettParesh Vyas
Sep 25, 2019·Cold Spring Harbor Perspectives in Medicine·Maureen McNulty, John D Crispino
Jun 2, 2021·Journal of Thrombosis and Haemostasis : JTH·Paul SaultierMarjorie Poggi
Aug 11, 2021·Cell Communication and Signaling : CCS·Yingjie QingHui Hui

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