Cystic Fibrosis Analysis

The abnormality in the CFTR gene alters the CFTR protein in people with cystic fibrosis. As a result, one hallmark of CF is the presence of a thick mucus secretion which clogs the bronchial tubes in the lungs and plugs the exit passages from pancreas and intestines, leading to loss of function of these organs.

CF happens because two parents have a defect in the CF transmembrane conductor regulator (CFTR) gene. If a child has only one parent that has a

CF is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CTFR) gene, which encodes a chloride ion channel that regulates osmotic balance across the epithelium through the transport of sodium ions and water4. Mutations

Cystic Fibrosis is a disorder where the exocrine glands secrete abnormally thick mucus, leading to obstruction of the pancreas and chronic infections of the lungs, which usually cause death in childhood or early adulthood. Some mildly affected patients may survive longer. Doctors can diagnose the disease by testing the patients perspiration because people with Cystic Fibrosis have high amounts of salt in their perspiration. Those with respiratory infections are treated with antibiotics, with aerosols that relieve constriction of the airways and liquefy the thick mucus, and by physical therapy to help patients cough up the obstructing secretions. Patients with pancreatic insufficiency can take pancreatic enzymes with meals.

Cystic fibrosis (CF) is an inherited disease that affects the lungs and digestive system (National Heart, Blood, and Lung Institute, 2013). CF is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene located on chromosome 7q31 (Beery & Workman, 2012, p. 192). More than 1600 different mutations in this gene have been identified, but 70% of cystic fibrosis patients have the amino acid ΔF508 defect. This mutation occurs when the CFTR protein is missing three nucleotides at position 508 which codes for the amino acid phenylalanine essential to nutrition (Scott, 2013, p. 493).

Cystic Fibrosis is a genetic disease that causes the body’s lungs to generate a different type of mucus than a non-infected body would. The contaminated lungs will produce mucus that is thick and adhesive which clogs the lungs and leads to an unpleasant and abhorrent lung infection. CF also interferes with the pancreas, disallowing the digestive enzymes from breaking down and absorbing food in the intestine. This can result in low nutrition, feeble growth, excessive sweat production, difficulties in breathing, and sometimes lung disease. When producing extra sweat and mucus, the body loses salt. If too much salt is lost, it can cause abnormal heart rhythms, disturbance of minerals in the blood, and perhaps, shock.

Since we have already known the amino sequence of the protein in previous step, we can narrow down the targeting ubiquitin ligase based on existing research data such as papers, NCBI data.

protein and it deletes a small amount of DNA from the CFTR gene. I am going to explain what

The Cystic Fibrosis Foundation [CFF] (2010) states the 1400 CFTR gene mutations are classified into 6 groups

The protein of the cystic fibrosis gene is called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). The gene is located on 7q31.2 long arm of chromosome 7 at position 31.2. The CF gene also has 27 exons and is made up of 250,000 DNA nucleotides. CFTR moves chloride ions out of cells which is very important for salt and water balances on the epithelial cells.

In 1989, the CFTR gene was discovered. (Discovery) This gene carries the instructions for the CFTR protein, which sits on the cell surface transporting chloride ions across the cell wall. When the CFTR gene is mutated, the CFTR protein is made incorrectly, and it is unable to exchange chloride ions. The high chlorine concentration inside of the cell is not optimal for normal cell function, so the lung cells naturally begin to pull in water from the mucus to dilute the thick chlorine concentration inside the cells. The result is thick, sticky mucus on the outside of the cells that mats down the cilia in lung airways. Clearing the throat and absorbing nutrients thus becomes extremely difficult and the symptoms of CF arise. (May)

Cystic Fibrosis (CF) is an autosomal recessive gene that causes a wide range of symptoms because there are over 1,000 changes or mutations that can occur within the cystic fibrosis transmembrane receptor (CFTR) protein. The CFTR protein is generally a chloride ion chain “regulated by cyclic adenosine monophosphate and therefore can act as a regulator of other electrolyte channels”(Grossman, S., & Grossman, L. 2005, p. 46). Typically this protein allows chloride ions to exit mucus-producing cells allowing water to flow in and thin the mucus. However, if the CFTR protein has been mutated, such as in cystic fibrosis, chloride ions cannot exit. This causes the mucus to thicken, become sticky, and obstruct the various channels it passes through. This build up of mucus also prevents bacteria from being cleaned from cells thoroughly increasing the patients risk for infections (Grossman, S., & Grossman, L. 2005). However, the severity of CF depends on whether the patients have complete or partial loss of the CFTR gene. If the person has the classic form of CF abnormalities of CFTR will commonly affect “…the respiratory, gastrointestinal, endocrine and metabolic, and genitourinary systems”(Schram, C. 2012). However, if people have atypical forms of CF their genetic disorder may only affect one of the organ systems and may not be found until the patient develops symptoms in their late childhood, early adolescence, or adulthood

The endoplasmic reticulum (ER) is an essential organelle that is a major place for the biogenesis of cellular components including proteins, lipids, and carbohydrates and internal calcium storage. ER is primarily responsible for protein translocation, protein folding and protein post modification. Proper folding of protein in the ER is accomplished with the aid of ER resident proteins or enzymes such as chaperones. Binding of chaperones to

Molecular chaperones stabilize unfolded or misfolded proteins until native conformations have been obtained to promote cell survival during and after stress conditions. They do not change or add to the folding principles encoded by a protein because polypeptide chains inherently carry within them all the information that is necessary for achieving the native state of a protein. Instead, they optimize the folding process by stabilizing folding intermediates and are involved in every aspect of proteome maintenance including de novo folding, refolding of stress-induced misfolded proteins, and targeting proteins for degradation (Hartl 2009, Hartl 2011). Chaperones, many of which are induced or upregulated only during stress conditions, work in cooperative networks when protein-aggregate concentration

The fluorescence of RepA70-YFP increased as more RepA70-CFP was produced (Fig. 3C), and this indicated that ClpAP protease could be overloaded and a proteolytic-queue forms similar to what was observed with the LAA tagged proteins targeted to ClpXP8. We also tested two other tags, MarA and MarAn20 (20 amino acids from the N-terminal of MarA), which target proteins to be degraded by the Lon protease. The Lon protease was weakly overloaded by MarA tagged proteins but was overloaded more by MarAn20 tagged proteins (Fig. 3C-D). This made us wonder if Lon could be overloaded when both MarA and MarAn20 were co-produced. Indeed, this was the case (Fig. 3E).