Proteasomal activator 28 gamma (PA28γ) upregulates the levels of HBx, a regulatory protein of hepatitis B virus (HBV) to stimulate HBV replication; however, the detailed mechanism remains unknown. Here, we found that PA28γ impaired the ability of seven in absentia homolog 1 (Siah-1) as an E3 ubiquitin ligase of HBx. PA28γ competitively inhibited the binding of Siah-1 to HBx in human hepatoma cells. Accordingly, PA28γ increased the stability of HBx and decreased HBx ubiquitination, abolishing the potential of Siah-1 to downregulate HBx levels. PA28γ also executed its role as an antagonist of Siah-1 during HBV replication, as demonstrated by an in vitro HBV replication system. The present study may provide insights into the mechanisms underlying the regulation of HBV replication.

蛋白酶体激活剂 28 γ (PA28γ) 上调 HBx 的水平，HBx 是乙型肝炎病毒 (HBV) 的一种调节蛋白，可刺激 HBV 复制；然而，详细的机制仍然未知。在这里，我们发现 PA28γ 损害了 7 个缺失同源物 1 (Siah-1) 作为 HBx 的 E3 泛素连接酶的能力。PA28γ 竞争性抑制人肝癌细胞中 Siah-1 与 HBx 的结合。因此，PA28γ 增加了 HBx 的稳定性并降低了 HBx 泛素化，消除了 Siah-1 下调 HBx 水平的潜力。PA28γ 在 HBV 复制过程中也发挥了其作为 Siah-1 拮抗剂的作用，如体外HBV 复制系统所证明的。本研究可能提供对 HBV 复制调控机制的深入了解。