Abstract
The functions of AML1 in hematopoietic differentiation are repressed by AML1-mutants including the AML1/ETO chimeric protein, which is seen in t(8;21) acute myeloid leukemia. Erythroid progenitors of the patients with t(8;21) AML expressed AML1/ETO. To investigate the effect of AML1/ETO in erythroid cells, we made a tetracycline-regulated AML1/ETO overexpression system in mouse erythroleukemic (MEL) cells. Enforced AML1/ETO repressed the terminal erythroid differentiation. Furthermore, we performed representational difference analysis using this MEL cell system to clone the downstream targets of AML1 in erythroid cell differentiation. We cloned a novel transmembrane protein, Art-1 (AML1-regulated transmembrane protein 1), which is a member of tetramembrane spanning superfamily. Art-1 expression was restricted in hematopoietic cells. It was upregulated by AML1 and downregulated by AML1/ETO in both erythroid and myeloid cells, and increased during erythroid cell differentiation. Art-1 may play an important role in the differentiation of erythroid cells, possibly as a direct downstream target of AML1.
Copyright 2001 Academic Press.
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Differentiation
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Cloning, Molecular
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Core Binding Factor Alpha 2 Subunit
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DNA-Binding Proteins / physiology*
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Enzyme Inhibitors / pharmacology
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Erythrocytes / metabolism*
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Erythrocytes / physiology
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Hydroxamic Acids / pharmacology
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Leukemia, Erythroblastic, Acute
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism*
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Membrane Proteins / physiology
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Mice
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Molecular Sequence Data
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Myeloid Cells / metabolism
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Oncogene Proteins, Fusion / biosynthesis
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Oncogene Proteins, Fusion / genetics
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Proto-Oncogene Proteins*
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RNA, Messenger / biosynthesis
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RUNX1 Translocation Partner 1 Protein
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Tetracycline / pharmacology
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Tissue Distribution
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Tumor Cells, Cultured
Substances
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AML1-ETO fusion protein, human
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Core Binding Factor Alpha 2 Subunit
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DNA-Binding Proteins
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Enzyme Inhibitors
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Hydroxamic Acids
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Membrane Proteins
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Oncogene Proteins, Fusion
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Tspan32 protein, mouse
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Proto-Oncogene Proteins
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RNA, Messenger
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RUNX1 Translocation Partner 1 Protein
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Runx1 protein, mouse
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Transcription Factors
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trichostatin A
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Tetracycline