title: Dual effects of HTLV-1 bZIP factor in suppression of interferon regulatory factor 1.
abstract: Human T-cell leukemia virus type-1 (HTLV-1) causes ATL in 2.5% of carriers after a long period of latent infection. Moreover, half of adult T-cell leukemia (ATL) patients succumb to this disease within 1year of onset. HTLV-1 bZIP factor (HBZ) is constitutively expressed in all the ATL cells. Thus, suggesting that HBZ may play a key role in cellular leukemogenesis. Herein we present evidence that interferon regulatory factor IRF-1, which is a member of IRF transcription family, interacts with HBZ. The N-terminal of HBZ interacted with IRF-1. HBZ reduced both IRF-1 DNA-binding activity and stability via a proteasome-dependent pathway. In addition, IRF-1-mediated apoptosis is significantly reduced by ectopic production of the HBZ. These results suggested that HBZ has dual suppressive effects on IRF-1 function, which may contribute to HTLV-1 related pathogenesis.
authors.affiliation: Faculty of Pharmaceutical Science at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Mukai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohshima
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D050856:Interferon Regulatory Factor-1; D046988:Proteasome Endopeptidase Complex