Cystic transmembrane regulator protein

Disorders caused by misfolded mutant proteins that fail to pass the quality control system of the ER (e.g., mutations of the cystic fibrosis transmembrane regulator protein (CFTR) causing cystic fibrosis). The mutant proteins are retrotranslocated into the cytosol and finally subjected to proteolysis. In some... 

The hypothesis that Pgp regulates volume-activated chloride channels was developed by the observation that Pgp was highly related to the cystic fibrosis transmembrane regulator protein (CFTR). CFTR belongs, like Pgp, to the ABC superfamily of transporters and is a plasma membrane chloride channel that is dysfunctional in cystic fibrosis (50). However, the role of Pgp in volume-regulatory processes has been controversial, and a current hypothesis is that Pgp does not have channel activity itself, but it may regulate swelling-induced anion channels (57). 

Cystic fibrosis, a disease of the Caucasian population, is associated with defective CL regulation and is essentially a disorder of epithehal cells (113,114). The defect arises at several levels in the CL ion transporter, ie, the cystic fibrosis transmembrane regulation (CFTR), and is associated with defective CL transport and defective processing, whereby the protein is not correctiy incorporated into the cell membrane. The most common mutation, affecting approximately 60% of patients, is termed F 608 and designates the loss of phenylalanine at this position. This mutation appears to be at least 50,000 years old, which suggests that its survival may have had evolutionary significance (115). 

A novel class of activators for chloride conductance in the cystic fibrosis transmembrane conductance regulator protein has been identified. These 3-(2-benzy-loxyphenyl)isoxazoles and 3-(2-benzyloxyphenyl)isoxazolines have been synthesized employing the 1,3-dipolar cycloaddition of nitrile oxides with various alkene and alkyne dipolarophiles (490). 

Cystic fibrosis is a life-threatening genetic disease caused by a dysfunctional cystic fibrosis transmembrane regulator, CFTR protein, which modulates salt and water transport into and out of cells. This ion-channel defect leads to poorly hydrated, thick, mucous secretions in the airways and severely impaired mucociliary func-... 

An effective gene therapy for patients with cystic fibrosis will require the delivery of cDNA encoding the cystic fibrosis transmembrane conductance regulator protein to the nucleus of the epithelial cells lining the bronchial trees within the lungs. Furthermore, an effective treatment could be achieved only if the transgene is... 

Ratjen E, Doring G. Cystic fibrosis. Lancet 2003 361 681-689. Brown CR, Hong-Brown LQ, Biwersi J, Verkman AS, Welch WJ. Chemical chaperones correct the mutant phenotype of the delta E508 cystic fibrosis transmembrane conductance regulator protein. Cell Stress Chaperones. 1996 1 117-125. 

The analysis of sweat for increased electrolyte concentration is used to confirm the diagnosis of cystic fibrosis (CF). CF is recognized as a syndrome with a wide spectrum of clinical presentations associated with a defect in the cystic fibrosis transmembrane conductance regulator protein (CFTR), a protein that normally regulates electrolyte transport across epithelial membranes. (For a more detailed discussion of CF, see Chapter 40.) Several hundred mutations of CFTR have been identified. Although mutational analysis is available, it is not informative in all cases, and the sweat test remains the standard for diagnostic testing. ... 

ABC transporters are involved in the transport of a wide variety of molecules. For example, cystic fibrosis is caused by a defective ABC transporter for chloride ion (cystic fibrosis transmembrane regulator. Chapter 12) and in Tangier s disease, the abnormality of cholesterol efflux is due to defects in an ABC protein (Chapter 20). 

Typhoid fever is caused by the entry of the pathogen S. typhi into gastrointestinal epithelial cells. This entry process is apparently mediated through the cystic fibrosis transmembrane regulator, a chloride channel of the ATP cassette family of proteins, since cells that expressed the mutant nonfunctional 508phenylanine deletion did not take up as much pathogen as wild-type cells (Pier et al., 1998). 

Solid-phase Zincke reaction was applied for the search of activators of the cystic fibrosis transmembrane conductance regulator protein. On the other hand, the tripeptide TRH (pGlu-His-Pro-NH2) was shown to be a hypothalamic releasing factor for the regulation of pituitary function. A solid-phase Zincke reaction was used to prepare analogues of TRH having the central histidine replaced with a 1,4-dihydropyridine unit (such as 48). Compound 48 was expected to cross the hydrophobic blood-brain barrier (BBB) but to be trapped within the central nervous system upon oxidation to the hydrophilic pyridinium form. 

The loss of three consecutive units of T from the gene that codes for CFTR, a transmembrane conductance regulator protein, results in the disease known as cystic fibrosis. Which amino acid is missing from CFTR to cause this disease ... 

The gene defective in cystic fibrosis codes for CFTR (cystic fibrosis transmembrane condnctance regulator), a membrane protein that pumps CP out of cells. If this CP pump is defective, CP ions remain in cells, which then take up water from the surrounding mucus by osmosis. The mucus thickens and accumulates in various organs, including the lungs, where its presence favors infections such as pneumonia. Left untreated, children with cystic fibrosis seldom survive past the age of 5 years. 

CF is caused by the absence of a protein called cystic fibrosis transmembrane conductance regulator (CFTR). This protein is required for the transport of chloride ions across cell membranes. On the molecular level, there is a mutation in the gene that encodes for CFTR. As a result, CFTR cannot be processed properly by the cell and is unable to reach the exocrine glands to assume its transport function. 

CFTR (cystic fibrosis transmembrane conductance regulator) a membrane protein that functions as a chloride channel. 

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