Characterization of the short isoform of Helios overexpressed in patients with T-cell malignancies.
In an earlier report, we demonstrated overexpression of a short isoform of Helios, Hel-5, which lacks three of four N-terminal zinc fingers, in patients with adult T-cell leukemia/lymphoma. Here, we characterized Hel-5 using immunoprecipitation, and gel shift and luciferase promoter assays, and found that Hel-5 lacks the repressor function observed with a full-length isoform of Helios. Moreover, Hel-5 associates with the full-length isoforms of the Ikaros gene family, Ikaros, Aiolos and Helios, and inhibits their DNA binding activity when present in excess, leading to dominant-negative effects on the full-length isoforms of the Ikaros gene family. Our results suggest a critical role for Helios in the mechanism of leukemogenesis.
Tabayashi
Takayuki
T
Department of Medicine, University of Okayama, 2-5-1 Shikatacho, Okayama 700-8558, Japan
Ishimaru
Fumihiko
F
Takata
Minoru
M
Kataoka
Itaru
I
Nakase
Koichi
K
Kozuka
Teruhiko
T
Tanimoto
Mitsune
M
D002460:Cell Line; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051740:Ikaros Transcription Factor / Q000145:classification / Q000235:genetics / Q000378:metabolism; D007938:Leukemia / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C111431:IKZF2 protein, human; D020033:Protein Isoforms; D014157:Transcription Factors; D051740:Ikaros Transcription Factor; D004247:DNA