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 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.
Section of Gene Function and Regulation, Institute of Cancer Research, London SW3 6JB, United Kingdom.
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Tsuzuki
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Towatari
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Saito
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D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D050989:GATA2 Transcription Factor; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation; D014178:Translocation, Genetic; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D020798:Two-Hybrid System Techniques
D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; C494712:Gata2 protein, mouse; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D014212:Tretinoin; D004247:DNA