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.
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 a 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.
Tsuzuki
Shinobu
S
Section of Gene Function and Regulation, Institute of Cancer Research, Chester Beatty Laboratories, London, United Kingdom.
Enver
Tariq
T
D001665:Binding Sites; D002460:Cell Line; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D050989:GATA2 Transcription Factor; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011485:Protein Binding; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism* / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D014178:Translocation, Genetic; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C118318:PLZF-RARalpha fusion protein, human; C492209:PLZF-RARalpha fusion protein, mouse; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012097:Repressor Proteins; D014157:Transcription Factors; C498646:ZBTB32 protein, human; C513267:Zbtb16 protein, mouse; C092037:ZBTB16 protein, human