Characterization of the short isoform of Helios overexpressed in patients with T‐cell malignancies
T Tabayashi, F Ishimaru, M Takata, I Kataoka… - Cancer …, 2007 - Wiley Online Library
T Tabayashi, F Ishimaru, M Takata, I Kataoka, K Nakase, T Kozuka, M Tanimoto
Cancer science, 2007•Wiley Online LibraryIn 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 …
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 …
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. (Cancer Sci 2007; 98: 182–188)
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