A “SYDE” effect of hierarchical phosphorylation: possible relevance to the cystic fibrosis basic defect

Since the identification of Cystic Fibrosis (CF) as a disease in 1938 until 2012, only therapies to treat symptoms rather than etiological therapies have been used to treat the disease. Over the last few years, new technologies have been developed, and gene editing strategies are now moving toward a one-time cure. This review will summarize recent advances in etiological therapies that target the basic defect in the CF Transmembrane Receptor (CFTR), the protein that is mutated in CF. We will discuss how newly identified compounds can directly target mutated CFTR to improve its function. Moreover, we will discuss how proteostasis regulators can modify the environment in which the mutant CFTR protein is synthesized and decayed, thus restoring CFTR function. The future of CF therapies lies in combinatory therapies that may be personalized for each CF patient.

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The basic defect in cystic fibrosis

Science ◽

10.1126/science.2544028 ◽

1989 ◽

Vol 244 (4911) ◽

pp. 1423-1423 ◽

Cited By ~ 7

Author(s):

I. Levitan

Keyword(s):

Cystic Fibrosis ◽

Basic Defect

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Defective Regulation of Epithelial Cl- Permeability and Protein Secretion in Cystic Fibrosis: The Putative Basic Defect

American Journal of Kidney Diseases ◽

10.1016/s0272-6386(89)80216-1 ◽

1989 ◽

Vol 14 (4) ◽

pp. 333-338 ◽

Cited By ~ 1

Author(s):

Kevin L. Kirk

Keyword(s):

Cystic Fibrosis ◽

Protein Secretion ◽

Basic Defect ◽

Cl Permeability

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Cystic fibrosis

10.1093/med/9780199568741.003.0132 ◽

2018 ◽

Author(s):

Rowland J. Bright-Thomas ◽

Andrew M. Jones

Keyword(s):

Cystic Fibrosis ◽

Gastrointestinal Tract ◽

Reproductive System ◽

Autosomal Recessive ◽

Pulmonary Infection ◽

Autosomal Recessive Disorder ◽

Carrier State ◽

Male Reproductive System ◽

Morbidity And Mortality ◽

Basic Defect

Cystic fibrosis is the most common lethal autosomal recessive disorder in Caucasians. There is no known survival advantage of the heterozygote carrier state. Chronic progressive pulmonary infection and bronchiectasis are the major causes of morbidity and mortality. The disease affects all ductal systems where the basic defect is manifest, including the pancreas, gastrointestinal tract, sinuses, hepatobiliary system, and male reproductive system, and has significant effects on nutrition and growth.

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RNA Methylation—A Possible Genetic Marker in Cystic Fibrosis

PEDIATRICS ◽

10.1542/peds.50.3.485 ◽

1972 ◽

Vol 50 (3) ◽

pp. 485-487

Author(s):

Owen M. Rennert ◽

Richard L. Julius ◽

David LaPointe

Keyword(s):

Cystic Fibrosis ◽

Cell Culture ◽

Genetic Marker ◽

Inborn Error ◽

Cultured Cells ◽

Inborn Error Of Metabolism ◽

Initial Report ◽

Rna Methylation ◽

Basic Defect ◽

Cell Culture Systems

Cystic fibrosis (CF) of the pancreas was initially thought to be an inborn error of metabolism affecting only exocrine tissue. In 1969, the demonstration by Danes and Bearn1 of metachromasia in cultivated fibroblasts obtained from patients with CF gave experimental support to the hypothesis that all CF cells reflect the basic biochemical defect. After this initial report several investigators observed that tissue cultured cells from some patients with CF and heterozygotes accumulated increased quantities of acid mucopolysaccharides and glycogen. No basic defect in these cell culture systems has been identified. No definitive test for the detection of the heterozygote state is available. See table in the PDF file

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