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

The hematopoietically expressed GATA family of transcription factors functi on as key regulators of blood cell fate. Among these, GATA-2 is implicated in the survival and growth of multipotential progenitors. Here we report th at the promyelocytic leukemia protein (PML) can complex with GATA-2 and pot entiate its transactivation capacity. The binding is mediated through inter action of the zinc finger region of GATA-2 and the B-box domain of PML. The B-bos region of PML is retained in the PML-RAR alpha (retinoic acid recept or alpha) fusion protein generated by the t(15;17) translocation characteri stic of acute promyelocytic leukemia (APL). Consistent with this, we provid e evidence that GATA-2 can physically associate with PML-RAR alpha. Functio nal 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 pa thogenesis of APL.