Cancer Research UK, School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Virology. 2011 Dec 20;421(2):149-58. doi: 10.1016/j.virol.2011.09.025. Epub 2011 Oct 21.
Proteasomes represent the major non-lysosomal mechanism responsible for the degradation of proteins. Following interferon γ treatment 3 proteasome subunits are replaced producing immunoproteasomes. Adenovirus E1A interacts with components of the 20S and 26S proteasome and can affect presentation of peptides. In light of these observations we investigated the relationship of AdE1A to the immunoproteasome. AdE1A interacts with the immunoproteasome subunit, MECL1. In contrast, AdE1A binds poorly to the proteasome β2 subunit which is replaced by MECL1 in the conversion of proteasomes to immunoproteasomes. Binding sites on E1A for MECL1 correspond to the N-terminal region and conserved region 3. Furthermore, AdE1A causes down-regulation of MECL1 expression, as well as LMP2 and LMP7, induced by interferon γ treatment during Ad infections or following transient transfection. Consistent with previous reports AdE1A reduced IFNγ-stimulated STAT1 phosphorylation which appeared to be responsible for its ability to reduce expression of immunoproteasome subunits.
蛋白酶体是负责蛋白质降解的主要非溶酶体机制。干扰素 γ 处理后，有 3 种蛋白酶体亚基被替换，产生免疫蛋白酶体。腺病毒 E1A 与 20S 和 26S 蛋白酶体的成分相互作用，可影响肽的呈递。鉴于这些观察结果，我们研究了 AdE1A 与免疫蛋白酶体的关系。AdE1A 与免疫蛋白酶体亚基 MECL1 相互作用。相比之下，AdE1A 与蛋白酶体 β2 亚基结合不良，在蛋白酶体转化为免疫蛋白酶体的过程中，MECL1 取代了蛋白酶体 β2 亚基。E1A 上与 MECL1 结合的位点对应于 N 端区域和保守区域 3。此外，AdE1A 导致干扰素 γ 处理诱导的感染或瞬时转染后 MECL1 表达以及 LMP2 和 LMP7 的下调。与之前的报道一致，AdE1A 降低了 IFNγ 刺激的 STAT1 磷酸化，这似乎是其降低免疫蛋白酶体亚基表达能力的原因。
