Faculty of Pharmaceutical Science at Kagawa Campus, Tokushima Bunri University, Kagawa, Japan.
J Cell Biochem. 2010 Sep 1;111(1):187-94. doi: 10.1002/jcb.22687.
HTLV-1 infection causes adult T-cell leukemia (ATL). The development of ATL is thought to be associated with disruption of transcriptional control of cellular genes. HTLV-1 basic leucine-zipper (bZIP) factor, HBZ, is encoded by the complementary strand of the provirus. We previously reported that HBZ interacts with c-Jun and suppresses its transcriptional activity. To identify the cellular factor(s) that interact with HBZ, we conducted a yeast two-hybrid screen using full-length HBZ as bait and identified MafB. HBZ heterodimerizes with MafB via each bZIP domain. Luciferase analysis revealed a significant decrease in transcription through Maf recognition element (MARE) in a manner dependent on the bZIP domain of HBZ. Indeed, production of full-length HBZ in cells decreased the MARE-bound MafB protein, indicating that HBZ abrogates the DNA-binding activity of MafB. In addition, HBZ reduced the steady-state levels of MafB, and the levels were restored by treatment with a proteasome inhibitor. These results suggest a suppressive effect of HBZ on Maf function, which may have a significant role in HTLV-1 related pathogenesis.
HTLV-1 感染可引起成人 T 细胞白血病（ATL）。ATL 的发生被认为与细胞基因转录控制的破坏有关。HTLV-1 碱性亮氨酸拉链（bZIP）因子 HBZ 由前病毒的互补链编码。我们之前报道 HBZ 与 c-Jun 相互作用并抑制其转录活性。为了鉴定与 HBZ 相互作用的细胞因子，我们使用全长 HBZ 作为诱饵进行酵母双杂交筛选，鉴定出 MafB。HBZ 通过各自的 bZIP 结构域与 MafB 异二聚化。荧光素酶分析显示，通过依赖于 HBZ 的 bZIP 结构域的方式，转录通过 Maf 识别元件（MARE）显著减少。事实上，细胞中全长 HBZ 的产生降低了 MARE 结合的 MafB 蛋白，表明 HBZ 破坏了 MafB 的 DNA 结合活性。此外，HBZ 降低了 MafB 的稳定水平，并且通过用蛋白酶体抑制剂处理可以恢复水平。这些结果表明 HBZ 对 Maf 功能具有抑制作用，这可能在 HTLV-1 相关发病机制中具有重要作用。
