HBx is a short-lived protein whose rapid turnover is mainly regulated by ubiquitin-dependent proteasomal degradation pathways. Our prior work identified BAF155 to be one of the HBx binding partners. Since BAF155 has been shown to stabilize other members of the SWI/SNF chromatin remodelling complex by attenuating their proteasomal degradation, we proposed that BAF155 might also contribute to stabilizing HBx protein in a proteasome-dependent manner. Here we report that BAF155 protected hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation by competing with the 20S proteasome subunit PSMA7 to bind to HBx. BAF155 was found to directly interact with HBx via binding of its SANT domain to the HBx region between amino acid residues 81 and 120. Expression of either full-length BAF155 or SANT domain increased HBx protein levels whereas siRNA-mediated knockdown of endogenous BAF155 reduced HBx protein levels. Increased HBx stability and steady-state level by BAF155 were attributable to inhibition of ubiquitin-independent and PSMA7-mediated protein degradation. Consequently, overexpression of BAF155 enhanced the transcriptional transactivation function of HBx, activated protooncogene expression and inhibited hepatoma cell clonogenicity. These results suggest that BAF155 plays important roles in ubiquitin-independent degradation of HBx, which may be related to the pathogenesis and carcinogenesis of HBV-associated HCC.

中文翻译：

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染色质重塑因子BAF155保护乙型肝炎病毒X蛋白（HBx）不受泛素依赖性蛋白酶体降解。

HBx是一种短暂的蛋白质，其快速更新主要受泛素依赖性蛋白酶体降解途径调控。我们先前的工作确定BAF155是HBx结合伙伴之一。由于已显示BAF155通过减缓其蛋白酶体降解来稳定SWI / SNF染色质重塑复合体的其他成员，因此我们建议BAF155可能还以蛋白酶体依赖性方式有助于稳定HBx蛋白。在这里，我们报道BAF155通过与20S蛋白酶体亚基PSMA7竞争结合HBx，保护了B型肝炎病毒X蛋白（HBx）不受泛素依赖性蛋白酶体降解。发现BAF155通过其SANT结构域与氨基酸残基81和120之间的HBx区结合直接与HBx相互作用。全长BAF155或SANT结构域的表达增加了HBx蛋白水平，而siRNA介导的内源BAF155的敲低降低了HBx蛋白水平。BAF155增加的HBx稳定性和稳态水平归因于泛素依赖性和PSMA7介导的蛋白质降解的抑制。因此，BAF155的过表达增强了HBx的转录反式激活功能，激活了原癌基因的表达并抑制了肝癌细胞的克隆性。这些结果表明，BAF155在不依赖泛素的HBx降解中起重要作用，这可能与HBV相关HCC的发病机理和致癌作用有关。BAF155增加的HBx稳定性和稳态水平归因于泛素依赖性和PSMA7介导的蛋白质降解的抑制。因此，BAF155的过表达增强了HBx的转录反式激活功能，激活了原癌基因的表达并抑制了肝癌细胞的克隆性。这些结果表明，BAF155在不依赖泛素的HBx降解中起重要作用，这可能与HBV相关HCC的发病机理和致癌作用有关。BAF155增加的HBx稳定性和稳态水平归因于泛素依赖性和PSMA7介导的蛋白质降解的抑制。因此，BAF155的过表达增强了HBx的转录反式激活功能，激活了原癌基因的表达并抑制了肝癌细胞的克隆性。这些结果表明，BAF155在不依赖泛素的HBx降解中起重要作用，这可能与HBV相关HCC的发病机理和致癌作用有关。