Dual effects of HTLV-1 bZIP factor in suppression of interferon regulatory factor 1
Dual effects of HTLV-1 bZIP factor in suppression of interferon regulatory factor 1
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DOI：
10.1016/j.bbrc.2011.05.014
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发表时间：
2011-06-03
影响因子：
3.1
通讯作者：
Ohshima, Takayuki
中科院分区：
文献类型：
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作者：
Mukai, Risa;Ohshima, Takayuki
人类 T 细胞白血病病毒 1 型 (HTLV-1) 在长期潜伏感染后，会导致 2.5% 的携带者出现 ATL。此外，一半的成人 T 细胞白血病 (ATL) 患者在发病后 1 年内死于这种疾病。 HTLV-1 bZIP 因子 (HBZ) 在所有 ATL 细胞中组成型表达。因此，表明HBZ可能在细胞白血病发生中发挥关键作用。在此，我们提供证据表明干扰素调节因子 IRF-1（IRF 转录家族的成员）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 IRF-1 DNA 结合活性和稳定性。此外，HBZ 的异位产生显着减少了 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相关的发病机制。 (C) 2011 Elsevier Inc. 保留所有权利。
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 1 year 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. (C) 2011 Elsevier Inc. All rights reserved.