The COP9 signalosome controls ubiquitinylation of ABCA1
The COP9 signalosome controls ubiquitinylation of ABCA1
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DOI：
10.1016/j.bbrc.2009.02.161
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发表时间：
2009-04-24
影响因子：
3.1
通讯作者：
Ueda, Kazumitsu
中科院分区：
文献类型：
--
作者：
Azuma, Yuya;Takada, Mie;Ueda, Kazumitsu
ATP 结合盒蛋白 A1 (ABCA1) 介导细胞游离胆固醇和磷脂转移至血浆中的细胞外受体载脂蛋白 A-1 (apoA-1)，形成高密度脂蛋白 (HDL)。 ABCA1被认为在负载胆固醇的巨噬细胞中被蛋白酶体降解，然而，ABCA1蛋白酶体降解的机制和调控仍不清楚。在这项研究中，我们分析了 ABCA1 和 CON 信号体 (CSN) 之间的假定相互作用，CSN 是控制蛋白质泛素化和去泛素化的关键分子。 CSN2 和 CSN5（COP9 CSN 复合体的亚基）在 HEK293 细胞中共表达时与 ABCA1 共沉淀，并且蛋白酶体降解被 MG132 抑制。 CSN2 的过表达增加了内源性 CSN7 和 CSN8，并减少了 ABCA1 的泛素化形式。这些结果表明CSN是控制ABCA1泛素化和去泛素化的关键分子，因此是开发预防动脉粥样硬化的潜在药物的重要靶点。 (C) 2009 Elsevier Inc. 保留所有权利。
ATP-binding cassette Protein A1 (ABCA1) mediates the transfer of cellular free cholesterol and phospholipids to apolipoprotein A-1 (apoA-1), an extracellular acceptor in plasma, to form high-density lipoprotein (HDL). ABCA1 has been Suggested to be degraded by proteasome in cholesterol-loaded macrophages, however, the mechanism and regulation of proteasomal degradation of ABCA1 remain unclear. In this Study, we analyzed the putative interaction between ABCA1 and CON signalosome (CSN), a key molecule in controlling protein ubiquitination and deubiquitination. CSN2 and CSN5, subunits of COP9 CSN cornplex, were coprecipitated with ABCA1 when coexpressed in HEK293 cells and proteasomal degradation was inhibited by MG132. Overexpression of CSN2 increased endogenous CSN7 and CSN8, and decreased ubiquitinylated forms of ABCA1. These results suggest that CSN is a key molecule which controls the Ubiquitinylation and deubiquitinylation of ABCA1, and is thus an important target for developing potential drugs to prevent atherosclerosis. (C) 2009 Elsevier Inc. All rights reserved.