CAND1 exchange factor promotes Keap1 integration into cullin 3-RING ubiquitin ligase during adipogenesis
CAND1 exchange factor promotes Keap1 integration into cullin 3-RING ubiquitin ligase during adipogenesis
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DOI：
10.1016/j.biocel.2015.07.013
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发表时间：
2015-09-01
影响因子：
4
通讯作者：
Naumann, Michael
中科院分区：
文献类型：
--
作者：
Dubiel, Dawadschargal;Ordemann, Juergen;Naumann, Michael
脂肪生成是由过多的调节蛋白控制的，这些蛋白通常由泛素蛋白酶体系统控制。在这里，我们发现LISA-2前脂肪细胞的分化与cullin相关和核苷酸解离的1(Candi)、COP9信号体(CSN)、neddylated cullin 3(CUL3)和BTB蛋白Keap1的增加有关。Candi的沉默导致Keap1与CUL3环泛素连接酶(CRL3)的整合减少和减少，从而延缓脂肪的形成。靶向miRNA148a的Candi瞬时转染LISA-2细胞也能降低Keap1，减缓LISA-2细胞的成脂。这些结果首次证明了Candi作为CRL3复合体的BTB-蛋白质交换因子。Neddylated CUL3的特异性增加可能是由于在脂肪形成过程中CUL3或CRL3在膜结合位置的募集。总之，这些结果表明，在LISA-2细胞的成脂过程中，发生了依赖CAND1的重塑和CRL3复合体的激活/缺失。(C)2015爱思唯尔有限公司。保留所有权利。
Adipogenesis is governed by a plethora of regulatory proteins which are most commonly controlled by the ubiquitin proteasome system. Here, we show that the differentiation of LiSa-2 preadipocytes is associated with an increase of cullin-associated and neddylation-dissociated 1 (CANDI), COP9 signalosome (CSN), neddylated cullin 3 (Cul3) and the BTB protein Keap1. Silencing of CANDI leads to a decrease and reduced integration of Keap1 into Cul3-RING ubiquitin ligases (CRL3) and to a retardation of adipogenesis. Transient transfection of LiSa-2 cells with CANDI targeting miRNA148a also reduces Keap1 and slowed down adipogenesis of LiSa-2 cells. These results demonstrate for the first time that CANDI acts as a BTB-protein exchange factor for CRL3 complexes. The specific increase of neddylated Cul3 might be explained by the recruitment of Cul3 or CRL3 in a membrane-bound location during adipogenesis. Together, the results show that during adipogenesis in LiSa-2 cells a CAND1-dependent remodeling and activation/neddylation of CRL3 complexes take place. (C) 2015 Elsevier Ltd. All rights reserved.