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Molecular and Cellular Biology, September 2000, p. 6276-6286, Vol. 20, No. 17
Section of Gene Function and Regulation,
Institute of Cancer Research, London SW3 6JB, United
Kingdom,1 and First Department of
Internal Medicine, Nagoya University School of Medicine, Nagoya
466-8550, Japan2
Received 10 April 2000/Accepted 22 May 2000
The hematopoietically expressed GATA family of transcription
factors function as key regulators of blood cell fate. Among these,
GATA-2 is implicated in the survival and growth of multipotential progenitors. Here we report that the promyelocytic leukemia protein (PML) can complex with GATA-2 and potentiate its transactivation capacity. The binding is mediated through interaction of the zinc finger region of GATA-2 and the B-box domain of PML. The B-box region
of PML is retained in the PML-RAR
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Potentiation of GATA-2 Activity through
Interactions with the Promyelocytic Leukemia Protein (PML) and the
t(15;17)-Generated PML-Retinoic Acid Receptor
Oncoprotein
(retinoic acid receptor alpha)
fusion protein generated by the t(15;17) translocation characteristic
of acute promyelocytic leukemia (APL). Consistent with this, we provide
evidence that GATA-2 can physically associate with PML-RAR
.
Functional experiments further demonstrated that this interaction has
the capacity to render GATA-dependent transcription inducible by
retinoic acid, raising the possibility that GATA target genes may be
involved in the molecular pathogenesis of APL.
*
Corresponding author. Mailing address: Section of Gene
Function and Regulation, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, United Kingdom. Phone: 44-20-7352-8133. Fax:
44-20-7352-3299. E-mail: tariq{at}icr.ac.uk.
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