CFTR EXPRESSION REGULATION BY THE UNFOLDED PROTEIN RESPONSE

被引:41
作者
Bartoszewski, Rafal [1 ]
Rab, Andras [1 ]
Fu, Lianwu [1 ]
Bartoszewska, Sylwia [1 ]
Collawn, James [1 ]
Bebok, Zsuzsa [1 ]
机构
[1] Univ Alabama Birmingham, Dept Cell Biol, Birmingham, AL 35294 USA
来源
METHODS IN ENZYMOLOGY, VOL 491: UNFOLDED PROTEIN RESPONSE AND CELLULAR STRESS, PT C | 2011年 / 491卷
关键词
TRANSMEMBRANE CONDUCTANCE REGULATOR; ENDOPLASMIC-RETICULUM STRESS; CYSTIC-FIBROSIS; DELTA-F508; CFTR; MESSENGER-RNA; CELL-LINES; ACTIVATION; DISEASE; IDENTIFICATION; DEGRADATION;
D O I
10.1016/B978-0-12-385928-0.00001-8
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel and key regulator of epithelial functions. Mutations in the CFTR gene lead to reduced or dysfunctional CFTR protein and cause cystic fibrosis (CF), a generalized exocrinopathy affecting multiple organs. In the airways, loss of CFTR function leads to thickened mucus, reduced mucociliary clearance, chronic infections, and respiratory failure. Common airway disorders such as bronchitis and chronic obstructive pulmonary disease (COPD) also present CF-like symptoms such as mucus congestion and chronic inflammation without mutations in CFTR. The primary risk factors for COPD and chronic bronchitis include environmental stress insults such as pollutants and infections that often result in hypoxic conditions. Furthermore, environmental factors such as cigarette smoke and reactive oxygen species have been implicated in reduced CFTR function. Activation of cellular stress responses by these factors promotes differential, stress-associated gene expression regulation. During our investigations on the mechanisms of CFTR expression regulation, we have shown that the ER stress response, the unfolded protein response (UPR), decreases CFTR expression at the transcriptional, translational, and maturational levels. Here, we provide a detailed description of the methods we employ to study CFTR expression regulation by the UPR. Similar approaches are applicable in studies on other genes and how they are affected by the UPR.
引用
收藏
页码:3 / 24
页数:22
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