Cystic fibrosis transmembrane regulator

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). 

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... 

In Cystic fibrosis a point mutation of the cystic fibrosis transmembrane regulator (CTFR) prevents transport of this molecule to the cell surface. Instead this otherwise functional molecule is degraded by the ERAD-ubiquitin proteasome pathway. 

O In CF, the cystic fibrosis transmembrane regulator (CFTR) chloride channel is dysfunctional and usually results in decreased chloride secretion and increased sodium absorption, leading to altered viscosity of fluid excreted by the exocrine glands and mucosal obstruction. 

Cystic fibrosis Cystic fibrosis transmembrane regulator... 

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-... 

Prenatal diagnosis and carrier detection of cystic fibrosis Cystic fibrosis is an autosomal recessive genetic disease resulting from mutations in the cystic fibrosis transmembrane regulator (CFTR)... 

Genetic testing for cystic fibrosis using PCR. CFTR = cystic fibrosis transmembrane regulator. 

Lim M, McKenzie K, Floyd AD, Kwon E, Zeitlin PL. 2004. Modulation of deltaF508 cystic fibrosis transmembrane regulator trafficking and function with 4-phenylbuty-rate and flavonoids. Am J Respir Cell Mol Biol 31 351-357. 

Moss, R. B., Rodman, D., Spencer, L. T., Aitken, M. L., Zeitlin, P. L., Waltz, D., Milla, C., Brody, A. S., Clancy, J. P., Ramsey, B., Hamblett, N. and Heald, A. E. (2004). Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs... 

CaMKI is located in cytoplasm and nuclei and is likely to participate in regulation of gene transcription. In vitro CaMKI phosphorylates substrates such as synapsin and the cystic fibrosis transmembrane regulator although its in vivo substrates are yet to be identified. CaMKI is activated by phosphorylation by CaMKK when both kinases are calcium and CaM bound. The 25-residue CaM-binding peptide of CaMKI forms an o -hehcal stmcture. Two hydrophobic residues are located at positions 1 and 14 (Trp-303 and Met-316). The peptide induces the bending of the central hehx with the interaction of both the N- and C-domains of CaM (pdb 1MXE). > 1... 

Vij N, Fang S, Zeitlin PL. Selective inhibition of endoplasmic reticulum-associated degradation rescues DeltaF508-cystic fibrosis transmembrane regulator and suppresses interleukin-8 levels therapeutic implications. J. Biol. Chem. 2006 281 17369-17378. 

Mucoviscidosis or cystic fibrosis (CF) is indeed one of the most common autosomal recessive diseases. It is characterized by the production of a viscous secretion in the excretory glands. Accordingly, pancreatic cystic fibrosis can be observed in the pancreatic area and cylindrical bronchiectases in the pulmonary area. The inspissation of bile and mucus leads to obstruction of the bile canaliculi and subsequently to cholestasis. The gene product is characterized as cystic fibrosis transmembrane regulator (CFTR). (252) The gene defect, which is located on chromosome 7, causes a disorder of the intracellular transport of chloride ions (probably also of chloride ion secretion) and thus triggers the occurrence of CF. The incidence of mucoviscidosis is about 1 2,000-4,500. 

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 is characterized by an imbalance in airway chloride ion concentrations due to the absence of cystic fibrosis transmembrane regulator (CFTR) receptor. Three approaches have been taken to the use of aerosols to treat this... 

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). 

CFTR cystic fibrosis transmembrane regulator FEF25%-75% forced expiratory volume from 25 to 75% of vital capacity... 

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). 

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