A hematopoietic-specific transmembrane protein, Art-1, is possibly regulated by AML1.
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.
Harada
Y
Y
Department of Hematology/Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Harada
H
H
Downing
J R
JR
Kimura
A
A
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D003001:Cloning, Molecular; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism* / Q000502:physiology; D006877:Hydroxamic Acids / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D000075142:RUNX1 Translocation Partner 1 Protein; D013752:Tetracycline / Q000494:pharmacology; D014018:Tissue Distribution; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured; D059470:Tetraspanins
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D008565:Membrane Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000075142:RUNX1 Translocation Partner 1 Protein; D013752:Tetracycline; D014157:Transcription Factors; C107844:AML1-ETO fusion protein, human; C417909:Tspan32 protein, mouse; D059470:Tetraspanins; C493726:Runx1 protein, mouse; C012589:trichostatin A