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.
Mol Cell Biol
; 20(17): 6276-86, 2000 Sep.
Article
em En
| MEDLINE
| ID: mdl-10938104
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Translocação Genética
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Cromossomos Humanos Par 15
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Cromossomos Humanos Par 17
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Proteínas Nucleares
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Proteínas de Fusão Oncogênica
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Receptores do Ácido Retinoico
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Proteínas de Ligação a DNA
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Proteínas de Neoplasias
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article