Tanguy Gaëlle, Drévillon Loïc, Arous Nicole, Hasnain Afia, Hinzpeter Alexandre, Fritsch Janine, Goossens Michel, Fanen Pascale
INSERM U841, Département de Génétique, Equipe 11, Hôpital Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, Créteil, F-94010, France.
Biochim Biophys Acta. 2008 Jun;1783(6):1189-99. doi: 10.1016/j.bbamcr.2008.01.010. Epub 2008 Jan 26.
Cystic fibrosis is mainly caused by mutations that interfere with the biosynthetic folding of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The aim of this study was to find cellular proteins interacting with CFTR and regulating its processing. We have used a genetic screen in yeast to identify such proteins and identified CSN5 that interacted with the third cytoplasmic loop of CFTR. CSN5 is the 5th component of the COP9 signalosome, a complex of eight subunits that shares significant homologies to the lid subcomplex of the 26S proteasome and controls the stability of many proteins. The present study shows that CSN5 associates with the core-glycosylated form of CFTR and suggests that this association targets misfolded CFTR to the degradative pathway. Identifying CSN5 as a new component of the degradative pathway is an important step towards the goal of unraveling the sorting between misfolded and correctly folded CFTR proteins.
囊性纤维化主要由干扰囊性纤维化跨膜传导调节因子（CFTR）蛋白生物合成折叠的突变引起。本研究的目的是寻找与CFTR相互作用并调节其加工过程的细胞蛋白。我们利用酵母中的遗传筛选来鉴定此类蛋白，并鉴定出与CFTR的第三个细胞质环相互作用的CSN5。CSN5是COP9信号体的第5个组分，COP9信号体是一个由八个亚基组成的复合体，与26S蛋白酶体的盖子亚复合体具有显著同源性，并控制许多蛋白质的稳定性。本研究表明，CSN5与CFTR的核心糖基化形式相关联，并表明这种关联将错误折叠的CFTR靶向降解途径。将CSN5鉴定为降解途径的一个新组分是朝着解开错误折叠和正确折叠的CFTR蛋白之间分选目标迈出的重要一步。
