Degradation of polyomavirus JC T-antigen by stress involves the LIP isoform of C/EBPβ
Degradation of polyomavirus JC T-antigen by stress involves the LIP isoform of C/EBPβ
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DOI：
10.1080/15384101.2015.1042631
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发表时间：
2015-07-03
期刊：
影响因子：
4.3
通讯作者：
Wollebo, Hassen S.
中科院分区：
文献类型：
--
作者：
Bellizzi, Anna;White, Martyn K.;Wollebo, Hassen S.
内质网（ER）应激是由错误折叠或未折叠的蛋白质在内质网腔中的积累引起的。CCAAT/增强子结合蛋白是在ER应激期间表达上调的细胞蛋白之一。以前，我们已经确定了C/EBP β亚型，特别是LIP，作为多瘤病毒JC（JCV）的负调节因子，JCV是脱髓鞘疾病进行性多灶性白质脑病（PML）的病原体。在这里，我们表明，诱导ER应激毒胡萝卜素增加内源性LIP的表达和JCV转基因小鼠肿瘤细胞系中的JCV T抗原的降解。我们的研究结果还表明，LIP的过表达显着降低了T-Ag的水平，这种效果是逆转siRNA介导的沉默LIP。免疫沉淀/Western印迹实验表明LIP与T抗原直接相互作用。用MG 115（一种蛋白酶体抑制剂）处理过表达LIP的细胞，部分挽救了LIP介导的T抗原降解。我们的观察指出，在ER应激调节T抗原稳定性的作用，LIP可能打开一个新的途径，研究宿主病毒相互作用在ER应激。
Endoplasmic reticulum (ER) stress is caused by the accumulation of misfolded or unfolded proteins in the lumen of the endoplasmic reticulum. CCAAT/enhancer binding proteins are one of the cellular proteins whose expression is upregulated during ER stress. Previously, we have identified C/EBPbeta isoforms, especially LIP, as a negative regulator of polyomavirus JC (JCV), the causative agent of the demyelinating disease progressive multifocal leukoencephalopathy (PML). Here, we show that the induction of ER stress by thapsigargin increase the expression of endogenous LIP and the degradation of JCV T-antigen in a JCV-transgenic mouse tumor cell line. Our results also revealed that overexpression of LIP significantly reduced the level of T-Ag and this effect is reversed upon siRNA-mediated silencing of LIP. Immunoprecipitation/Western blot experiments indicated that LIP interacts with T-antigen directly. Treatment of cells that overexpress LIP with MG115, a proteasome inhibitor, partially rescued LIP-mediated degradation of T-antigen. Our observations point to a role of LIP in ER stress regulation of T-antigen stability and may open a new avenue to study host-virus interaction during ER stress.