Interactions of GATA-2 with the promyelocytic leukemia zinc finger (PLZF) protein, its homologue FAZF, and the t(11;17)-generated PLZF-retinoic acid receptor alpha oncoprotein

Abstract

Transcription factor GATA-2 Is Implicated in the survival and growth of multipotential progenitors. Here we report that the promyelocytic leukemia zinc finger (PLZF) protein can Interact with GATA-2 and can modify Its transactivation capacity. Fanconi anemia zinc finger (FAZF), a PLZF-homologous protein that has been variously described as ROG (repressor of GATA), and TZFP (testis zinc finger protein) also Interact with GATA-2. The zinc finger region of GATA-2 Is required for binding to PLZF and FAZF, but distinct Interfaces on the PLZF and FAZF molecules mediate the Interaction, suggesting that GATA-2 activity Is controlled by these 2 homologous proteins through distinct mechanisms. GATA-2 can also physically associate with the PLZF-RARalpha fusion protein generated by the t(11;17) chromosomal translocation associated with acute promyelocytic leukemia (APL). Functional experiments showed that this Interaction has the capacity to render GATA-dependent transcription responsive to treatment with ill combination of all-trans retinoic acid and the histone deacetylase Inhibitor trichostatin A (TSA). This combination of drugs has been shown to stimulate the terminal differentiation of leukemic t(11;17)-associated APL blasts, raising the possibility that GATA target genes may be Involved In the molecular pathogenesis of APL. (C) 2002 by The American Society of Hematology.