Open AccessCharacterization of the short isoform of Helios overexpressed in patients with T‐cell malignancies
Author(s) -
Tabayashi Takayuki,
Ishimaru Fumihiko,
Takata Minoru,
Kataoka Itaru,
Nakase Koichi,
Kozuka Teruhiko,
Tanimoto Mitsune
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2006.00372.x
Subject(s) - gene isoform , gene , immunoprecipitation , biology , repressor , microbiology and biotechnology , gene family , gene expression , cancer research , genetics
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)