The ets family member Tel binds to the Fli-1 oncoprotein and inhibits its transcriptional activity.
The tel gene, recently shown to be translocated in a spectrum of acute and chronic human leukemias, belongs to the ets family of sequence-specific transcription factors. To determine the role of Tel in normal hematopoietic development, we used the tel gene as the bait in the yeast two-hybrid system to screen a hematopoietic stem cell library. Two partners were identified: Tel binds to itself, and Tel binds to the ets family member Fli-1. In vitro and in vivo assays confirmed these interactions. In transient transfection assays, Fli-1 transactivates megakaryocytic specific promoters, and Tel inhibits this effect of Fli-1. Transactivation studies using deletion mutants of Tel, and the Tel-AML-1 fusion protein, indicate that the helix-loop-helix domain of Tel only partially inhibits transactivation and that complete inhibition requires the full-length Tel molecule, including the DNA binding domain. The Tel and Fli-1 proteins are expressed early in hematopoiesis, and the inability of Tel fusion proteins such as Tel-AML-1 to counteract Fli-1 mediated transactivation may contribute to the malignant phenotype in human leukemias where this fusion protein is present.
Kwiatkowski
B A
BA
Medical Research Service, Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108, USA.
Bastian
L S
LS
Bauer
T R
TR
Tsai
S
S
Zielinska-Kwiatkowska
A G
AG
Hickstein
D D
DD
D001483:Base Sequence; D002454:Cell Differentiation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D016366:Open Reading Frames; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D015534:Trans-Activators / Q000037:antagonists & inhibitors*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D000097764:ETS Translocation Variant 6 Protein
D017931:DNA Primers; D004268:DNA-Binding Proteins; D016298:Hematopoietic Cell Growth Factors; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein