Elf-2, a rhombotin-2 binding ets transcription factor: discovery and potential role in T cell leukemia.
Rhombotin-2 (RBTN-2) is a proto-oncogene only in the context of T lymphocytes. We postulated that the oncogenic effect of RBTN-2 in T cells is likely mediated by binding protein(s) with T cell-specific expression. By screening a T cell cDNA library, we identified a novel ets transcription factor that binds RBTN-2. This protein was named elf-2 because its DNA-binding domain is virtually identical to that of ets family member elf-1. Northern analyses showed similar levels of two elf-2 transcripts (3.5 kb and 3.8 kb) in all tissues except thymus. Thymocytes expressed four- to 10-fold greater amounts of the 3.5 kb transcript than other tissues. Sequence analyses of cDNA clones indicated that these transcripts encode proteins differing only at their amino termini, and likely represent alternatively spliced isoforms. These isoforms (elf-2a and elf-2b) contain identical RBTN-2 binding regions and DNA-binding domains. Elf-2b lacks a putative transactivation domain. The expression patterns suggest that RBTN-2 normally interacts equally with elf-2a and elf-2b. In contrast, when RBTN-2 is inappropriately expressed in T cells, RBTN-2 would interact predominantly with elf-2b; this interaction may lead to T cell proliferation.
Wilkinson
D A
DA
Department of Virology and Molecular Biology, St Jude Children's Research Hospital, University of Tennessee, Memphis 38101, USA.
Neale
G A
GA
Mao
S
S
Naeve
C W
CW
Goorha
R M
RM
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D060588:LIM Domain Proteins; D015458:Leukemia, T-Cell / Q000378:metabolism*; D008667:Metalloproteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000737:chemistry*; D014157:Transcription Factors / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015003:Yeasts
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C103652:Elf2 protein, mouse; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; C513188:Lmo2 protein, mouse; C000715470:MAS1 protein, human; D008667:Metalloproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors