Posttranslational modifications add diversity to protein function. Throughout its life cycle, the cystic fibrosis transmembrane conductance regulator (CFTR) undergoes numerous covalent posttranslational modifications (PTMs), including glycosylation, ubiquitination, sumoylation, phosphorylation, and palmitoylation. These modifications regulate key steps during protein biogenesis, such as protein folding, trafficking, stability, function, and association with protein partners and therefore may serve as targets for therapeutic manipulation. More generally, an improved understanding of molecular mechanisms that underlie CFTR PTMs may suggest novel treatment strategies for CF and perhaps other protein conformational diseases. This review provides a comprehensive summary of co- and posttranslational CFTR modifications and their significance with regard to protein biogenesis.
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http://dx.doi.org/10.1152/ajplung.00431.2015 | DOI Listing |
J Transl Med
January 2025
Department of Hematology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Background: Targeting exportin1 (XPO1) with Selinexor (SEL) is a promising therapeutic strategy for patients with multiple myeloma (MM). However, intrinsic and acquired drug resistance constitute great challenges. SEL has been reported to promote the degradation of XPO1 protein in tumor cells.
View Article and Find Full Text PDFCell Commun Signal
January 2025
School of Basic Medical Sciences, Hubei University of Science and Technology, Hubei, 437000, China.
Autophagy dysfunction is associated with changes in autophagy-related genes. Various factors are connected to autophagy, and the mechanism regulating autophagy is highly complicated. Epigenetic changes, such as aberrant expression of histone demethylase, are actively associated not only with oncogenesis but also with inflammatory responses.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Functionally derivatized analogs of prenyl lipids are valuable tools for the detection and analysis of prenylated proteins. Using a biotinylated analog of geranylgeranyl, we previously identified Ykt6 as a substrate for a novel protein prenyltransferase, termed geranylgeranyltransferase type III (GGTase-III). Ykt6 is an evolutionarily highly conserved SNARE protein that regulates multiple intracellular trafficking pathways, including intra-Golgi trafficking and autophagosome-lysosome fusion.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Sheffield Institute for Translational Neuroscience, Division of Neuroscience, University of Sheffield, Sheffield, S10 2HQ, UK.
Determining the structure-function relationships of protein aggregates is a fundamental challenge in biology. These aggregates, whether formed in vitro, within cells, or in living organisms, present significant heterogeneity in their molecular features such as size, structure, and composition, making it difficult to determine how their structure influences their functions. Interpreting how these molecular features translate into functional roles is crucial for understanding cellular homeostasis and the pathogenesis of various debilitating diseases like Alzheimer's and Parkinson's.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
School of Forensic Medicine, Guizhou Medical University, Guiyang, China.
Deubiquitinating enzymes (DUBs) are integral regulators of protein stability. Among these, Ubiquitin-specific protease 18 (USP18) has emerged as a potential therapeutic target for heart failure. However, its precise role in atherosclerosis remains to be comprehensively understood.
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