Rearranged NF-kappa B2 gene in an adult T-cell leukemia cell line.
Adult T-cell leukemia (ATL) is an aggressive type of leukemia, originating from T-cells infected with human T-cell leukemia virus type 1. Accumulating evidence suggests the aberrant activation of NF-kappaB to be a causative factor mediating the abnormal proliferation of leukemic cells, thus resulting in the development of ATL. A rearranged NF-kappa B2/p100 gene was isolated from an ATL-derived cell line, which was generated by a chromosomal translocation. The isolated NF-kappa B2 mutant is fused with the with no (lysine) deficient protein kinase 1 gene, coding for a 58 kDa protein that retains the DNA binding Rel homology domain, but it lacks the entire ankyrin repeat inhibitory domain, thus suggesting its constitutive activation. This rearranged NF-kappa B2 gene product (p58) was localized in the nucleus, and formed a complex with NF-kappaB p65 or RelB. Moreover, a T-cell line expressing p58 increased the amount of an NF-kappa B2-inducible gene, NF-kappa B2/p100 by itself. These results suggest that such NF-kappa B2 gene rearrangement may therefore be a factor in the constitutive activation of NF-kappaB in ATL, and thereby playing a role in the ATL pathogenesis.
Isogawa
Masato
M
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan.
Higuchi
Masaya
M
Takahashi
Masahiko
M
Oie
Masayasu
M
Mori
Naoki
N
Tanaka
Yuetsu
Y
Aoyagi
Yutaka
Y
Fujii
Masahiro
M
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D019281:Dimerization; D015723:Gene Library; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D051379:Mice; D009154:Mutation; D052003:NF-kappa B p52 Subunit / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D051841:Transcription Factor RelB / Q000378:metabolism; D014178:Translocation, Genetic
D052003:NF-kappa B p52 Subunit; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; D051550:I-kappa B Kinase