The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated anion channel, which is expressed on the apical plasma membrane (PM) of epithelial cells. Mutations in the CFTR gene cause cystic fibrosis (CF), one of the most common genetic diseases among Caucasians. Most CF-associated mutations result in misfolded CFTR proteins that are degraded by the endoplasmic reticulum quality control (ERQC) mechanism. However, the mutant CFTR reaching the PM through therapeutic agents is still ubiquitinated and degraded by the peripheral protein quality control (PeriQC) mechanism, resulting in reduced therapeutic efficacy. Moreover, certain CFTR mutants that can reach the PM under physiological conditions are degraded by PeriQC. Thus, it may be beneficial to counteract the selective ubiquitination in PeriQC to enhance therapeutic outcomes for CF. Recently, the molecular mechanisms of CFTR PeriQC have been revealed, and several ubiquitination mechanisms, including both chaperone-dependent and -independent pathways, have been identified. In this review, we will discuss the latest findings related to CFTR PeriQC and propose potential novel therapeutic strategies for CF.
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Phagocytosis involves the engulfment and digestion of detrimental foreign objects (e.g., microbes) by different immune cells of our body, such as macrophages. Lipids play an important role during this immunological process, and hence, microbes have found ways to hijack these lipid pathways during phagocytosis to evade the immune system. For further information, see the review in this issue by Saharan and Kamat, pages 1279–1287. Image provided by Siddhesh Shashikant Kamat.
The multiple ubiquitination mechanisms in CFTR peripheral quality control
Shogo Taniguchi, Ryosuke Fukuda, Tsukasa Okiyoneda; The multiple ubiquitination mechanisms in CFTR peripheral quality control. Biochem Soc Trans 28 June 2023; 51 (3): 1297–1306. doi: https://doi.org/10.1042/BST20221468
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