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Molecular and Cellular Biology, September 2000, p. 6276-6286, Vol. 20, No. 17
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 alpha  Oncoprotein

Shinobu Tsuzuki,1,2 Masayuki Towatari,2 Hidehiko Saito,2 and Tariq Enver1,*

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-RARalpha (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-RARalpha . 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.

Molecular and Cellular Biology, September 2000, p. 6276-6286, Vol. 20, No. 17
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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