title: Interaction between the homeodomain protein HOXC13 and ETS family transcription factor PU.1 and its implication in the differentiation of murine erythroleukemia cells.
abstract: Some of homeodomain proteins and the ETS family of transcription factors are involved in hematopoiesis. RT-PCR analysis revealed that the HOXC13 and PU.1 genes were expressed in murine erythroleukemia (MEL) cells and their levels decreased during DMSO-induced differentiation into erythroid cells. HOXC13 bound to the ETS domain of PU.1 through a region encompassing the C-terminal part of the homeodomain and the most C-terminal region and enhanced the transcriptional activity of PU.1. Enforced expression of HOXC13 in MEL cells resulted in the suppression of beta-globin gene expression. In MEL cells overexpressing HOXC13 and PU.1, which also inhibits the differentiation of MEL cells, no synergistic effect on the suppression of beta-globin gene expression was observed. However, in the presence of DMSO, the expression levels of the beta-globin gene in the cells overexpressing HOXC13 and PU.1 were, unexpectedly, higher than those in the cells overexpressing PU.1 alone. The levels of PU.1 protein were markedly decreased despite that the levels of mRNA were preserved in the cells overexpressing PU.1 and HOXC13. It was, thus, suggested that although HOXC13 negatively regulates the differentiation of MEL cells into erythroid cells, it antagonizes PU.1 possibly by down-regulation of PU.1 protein in the presence of a differentiation stimulus.
authors: Department of Biochemistry and Genome Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors: Toshiyuki
authors: T
authors: Yamada
authors: Takeshi
authors: T
authors: Shimizu
authors: Mitsuhiro
authors: M
authors: Suzuki
authors: Fumiko
authors: F
authors: Kihara-Negishi
authors: Naoki
authors: N
authors: Nanashima
authors: Takuya
authors: T
authors: Sakurai
authors: Yang
authors: Y
authors: Fan
authors: Miki
authors: M
authors: Akita
authors: Tsuneyuki
authors: T
authors: Oikawa
authors: Shigeki
authors: S
authors: Tsuchida
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004920:Erythropoiesis; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D051379:Mice; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C410305:HOXC13 protein, human