Leukemia-related transcription factor TEL accelerates differentiation of Friend erythroleukemia cells.
TEL belongs to a member of the ETS family transcription factors that represses transcription of target genes such as FLI-1. Although TEL is essential for establishing hematopoiesis in neonatal bone marrow, its role in erythroid lineage is not understood. To investigate a role for TEL in erythroid differentiation, we introduced TEL into mouse erythroleukemia (MEL) cells. Overexpressing wild-type-TEL in MEL cells enhanced differentiation induced by hexamethylene bisacetamide or dimethylsulfoxide, as judged by the increased levels of erythroid-specific delta-aminolevulinate synthase and beta-globin mRNAs. TEL bound to a corepressor mSin3A through the helix-loop-helix domain. A TEL mutant lacking this domain still bound to the ETS binding site, but lost its transrepressional effect. This mutant completely blocked erythroid differentiation in MEL cells. Moreover, it showed dominant-negative effects over TEL-mediated transcriptional repression and acceleration of erythroid differentiation. Endogenous TEL mRNA was found to increase during the first 3 days in differentiating MEL cells and drastically decrease thereafter. All these data suggest that TEL might play some role in erythroid cell differentiation.
Waga
Kazuo
K
Department of Hematology, Dokkyo University School of Medicine, Tochigi, Japan.
Nakamura
Yuichi
Y
Maki
Kazuhiro
K
Arai
Honoka
H
Yamagata
Tetsuya
T
Sasaki
Ko
K
Kurokawa
Mineo
M
Hirai
Hisamaru
H
Mitani
Kinuko
K
D000624:5-Aminolevulinate Synthetase / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D005622:Friend murine leukemia virus / Q000302:isolation & purification*; D005914:Globins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000473:pathology* / Q000821:virology; D051379:Mice; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D000097764:ETS Translocation Variant 6 Protein
D000624:5-Aminolevulinate Synthetase; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005914:Globins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein