Cancer-testis antigen HCA587/MAGE-C2 interacts with BS69 and promotes its degradation in the ubiquitin-proteasome pathway
Cancer-testis antigen HCA587/MAGE-C2 interacts with BS69 and promotes its degradation in the ubiquitin-proteasome pathway
复制标题
癌睾丸抗原 HCA587/MAGE-C2 与 BS69 相互作用并促进其在泛素蛋白酶体途径中的降解
DOI：
10.1016/j.bbrc.2014.05.078
复制
发表时间：
2014-07-11
影响因子：
3.1
通讯作者：
Yin, Yanhui
中科院分区：
文献类型：
--
作者：
Hao, Jiaqing;Shen, Rui;Yin, Yanhui
HCA587又名MAGE-C2，属于MAGE基因家族，其特点是具有保守的MAGE同源结构域，在多种类型的肿瘤中具有活性，而在除雄性生殖细胞外的正常组织中保持沉默。 HCA587 的生物学功能很大程度上未知。为了对其进行分析，我们尝试鉴定 HCA587 的蛋白质伙伴。我们从 HEK293 细胞中免疫纯化含有 HCA587 的复合物，并通过质谱鉴定出 BS69（一种潜在的肿瘤抑制因子）作为相关蛋白，随后的免疫沉淀和 GST 下拉测定证实了 HCA587 与 BS69 的相互作用。有趣的是，HCA587的过度表达促进了BS69的泛素化和蛋白酶体降解，而内源性HCA587的敲低则增加了BS69的蛋白水平。与 BS69 在负调节 LMP1 诱导的 NF-κ B 激活中的功能作用一致，HCA587 的过表达导致 LMP1 诱导的 IL-6 产生显着增强。这些数据表明HCA587是BS69的新负调节因子。 (C) 2014 Elsevier Inc. 保留所有权利。
HCA587, also known as MAGE-C2, belonging to the MAGE gene family which is characterized by a conserved MAGE Homology Domain, is active in various types of tumors and silent in normal tissues except in male germ-line cells. The biological function of HCA587 is largely unknown. To analyze it, we attempted to identify protein partners of HCA587. We immunopurified HCA587-containing complex from HEK293 cells and identified BS69, a potential tumor suppressor, as an associated protein by mass spectrometry, and the following Immunoprecipitation and GST pull-down assays confirmed HCA587 interaction with BS69. Interestingly, overexpression of HCA587 promoted ubiquitination and the proteasomal degradation of BS69 whereas knockdown of endogenous HCA587 increased the protein level of BS69. Consistent with a functional role for BS69 in negatively regulating LMP1-induced NF-kappa B activation, overexpression of HCA587 resulted in a significant enhancement of LMP1-induced IL-6 production. These data indicate that HCA587 is a new negative regulator of BS69. (C) 2014 Elsevier Inc. All rights reserved.