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PMID: 10938104 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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.

Molecular and cellular biology ·Vol. 20 ·No. 17 ·2000-09-00 ·Pages 6276-86

Tsuzuki S, Towatari M, Saito H, Enver T

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.

MeSH Terms
Animals COS Cells Cell Line Cell Nucleus/metabolism Chromosomes, Human, Pair 15 Chromosomes, Human, Pair 17 DNA/metabolism DNA-Binding Proteins/chemistry,metabolism GATA2 Transcription Factor Humans Leukemia, Promyelocytic, Acute/metabolism Mice Neoplasm Proteins/chemistry,metabolism Nuclear Proteins Oncogene Proteins, Fusion Plasmids/metabolism Precipitin Tests Promyelocytic Leukemia Protein Protein Binding Protein Structure, Tertiary Receptors, Retinoic Acid/metabolism Retinoic Acid Receptor alpha Transcription Factors/chemistry,metabolism Transcriptional Activation Translocation, Genetic Tretinoin/pharmacology Tumor Cells, Cultured Tumor Suppressor Proteins Two-Hybrid System Techniques
Chemicals
DNA-Binding Proteins GATA2 Transcription Factor GATA2 protein, human Gata2 protein, mouse Neoplasm Proteins Nuclear Proteins Oncogene Proteins, Fusion Pml protein, mouse Promyelocytic Leukemia Protein RARA protein, human Rara protein, mouse Receptors, Retinoic Acid Retinoic Acid Receptor alpha Transcription Factors Tumor Suppressor Proteins PML protein, human Tretinoin DNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Tsuzuki S
Section of Gene Function and Regulation, Institute of Cancer Research, London SW3 6JB, United Kingdom.
Towatari M
Saito H
Enver T
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.17.6276-6286.2000
Published
2000-09-00
Pages
6276-86
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC86102
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.20.17.6276-6286.2000 PMC Full Text View journal details
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