Faculty of Pharmaceutical Science at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan.
Biochem Biophys Res Commun. 2011 Jun 3;409(2):328-32. doi: 10.1016/j.bbrc.2011.05.014. Epub 2011 May 8.
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.
人类 T 细胞白血病病毒 1 型（HTLV-1）在潜伏感染很长一段时间后，会导致 2.5%的携带者发生 ATL。此外，半数成人 T 细胞白血病（ATL）患者在发病后 1 年内死亡。HTLV-1 bZIP 因子（HBZ）在所有 ATL 细胞中持续表达。因此，HBZ 可能在细胞白血病发生中起关键作用。在此，我们提供证据表明，IRF 转录因子家族的成员干扰素调节因子 IRF-1 与 HBZ 相互作用。HBZ 的 N 端与 IRF-1 相互作用。HBZ 通过蛋白酶体依赖性途径降低了 IRF-1 的 DNA 结合活性和稳定性。此外，HBZ 的异位产生显著降低了 IRF-1 介导的细胞凋亡。这些结果表明，HBZ 对 IRF-1 功能具有双重抑制作用，这可能有助于 HTLV-1 相关发病机制。
