Ribosomal Stalk Protein Silencing Partially Corrects the ΔF508-CFTR Functional Expression Defect
Publication Date
May 11, 2016
Journal
PLOS Biology
Authors
Guido Veit, Kathryn Oliver, Pirjo M. Apaja, Doranda Perdomo, et al
Volume
14
Issue
5
Pages
e1002462
DOI
https://dx.plos.org/10.1371/journal.pbio.1002462
Publisher URL
http://journals.plos.org/plosbiology/article?id=10.1371%2Fjournal.pbio.1002462
Scopus
84971520499
Mendeley
http://www.mendeley.com/research/ribosomal-stalk-protein-silencing-partially-corrects-%CE%B4f508cftr-functional-expression-defect
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Mendeley | Further Information

{"title"=>"Ribosomal Stalk Protein Silencing Partially Corrects the ΔF508-CFTR Functional Expression Defect", "type"=>"journal", "authors"=>[{"first_name"=>"Guido", "last_name"=>"Veit", "scopus_author_id"=>"57194736383"}, {"first_name"=>"Kathryn", "last_name"=>"Oliver", "scopus_author_id"=>"57189507254"}, {"first_name"=>"Pirjo M.", "last_name"=>"Apaja", "scopus_author_id"=>"8718060200"}, {"first_name"=>"Doranda", "last_name"=>"Perdomo", "scopus_author_id"=>"35748914000"}, {"first_name"=>"Aurélien", "last_name"=>"Bidaud-Meynard", "scopus_author_id"=>"55232353700"}, {"first_name"=>"Sheng Ting", "last_name"=>"Lin", "scopus_author_id"=>"57189504294"}, {"first_name"=>"Jingyu", "last_name"=>"Guo", "scopus_author_id"=>"55537232000"}, {"first_name"=>"Mert", "last_name"=>"Icyuz", "scopus_author_id"=>"26536039500"}, {"first_name"=>"Eric J.", "last_name"=>"Sorscher", "scopus_author_id"=>"7005699295"}, {"first_name"=>"John L.", "last_name"=>"Hartman IV", "scopus_author_id"=>"7201671366"}, {"first_name"=>"Gergely L.", "last_name"=>"Lukacs", "scopus_author_id"=>"35602405400"}], "year"=>2016, "source"=>"PLoS Biology", "identifiers"=>{"issn"=>"15457885", "scopus"=>"2-s2.0-84971520499", "sgr"=>"84971520499", "pui"=>"610547056", "pmid"=>"27168400", "doi"=>"10.1371/journal.pbio.1002462"}, "id"=>"1a1f4e83-b87f-3c63-aee6-0aff1d7d14d9", "abstract"=>"The most common cystic fibrosis (CF) causing mutation, deletion of phenylalanine 508 (ΔF508 or Phe508del), results in functional expression defect of the CF transmembrane conductance regulator (CFTR) at the apical plasma membrane (PM) of secretory epithelia, which is attributed to the degradation of the misfolded channel at the endoplasmic reticulum (ER). Deletion of phenylalanine 670 (ΔF670) in the yeast oligomycin resistance 1 gene (YOR1, an ABC transporter) of Saccharomyces cerevisiae phenocopies the ΔF508-CFTR folding and trafficking defects. Genome-wide phenotypic (phenomic) analysis of the Yor1-ΔF670 biogenesis identified several modifier genes of mRNA processing and translation, which conferred oligomycin resistance to yeast. Silencing of orthologues of these candidate genes enhanced the ΔF508-CFTR functional expression at the apical PM in human CF bronchial epithelia. Although knockdown of RPL12, a component of the ribosomal stalk, attenuated the translational elongation rate, it increased the folding efficiency as well as the conformational stability of the ΔF508-CFTR, manifesting in 3-fold augmented PM density and function of the mutant. Combination of RPL12 knockdown with the corrector drug, VX-809 (lumacaftor) restored the mutant function to ~50% of the wild-type channel in primary CFTRΔF508/ΔF508 human bronchial epithelia. These results and the observation that silencing of other ribosomal stalk proteins partially rescue the loss-of-function phenotype of ΔF508-CFTR suggest that the ribosomal stalk modulates the folding efficiency of the mutant and is a potential therapeutic target for correction of the ΔF508-CFTR folding defect.", "link"=>"http://www.mendeley.com/research/ribosomal-stalk-protein-silencing-partially-corrects-%CE%B4f508cftr-functional-expression-defect", "reader_count"=>34, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Librarian"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>11, "Other"=>3, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Librarian"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>11, "Other"=>3, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>8, "Agricultural and Biological Sciences"=>18, "Medicine and Dentistry"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Psychology"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Canada"=>1}, "group_count"=>0}

Scopus | Further Information

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  • {"unique-ip"=>"26", "full-text"=>"18", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"33", "full-text"=>"17", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"18", "full-text"=>"21", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"27", "full-text"=>"79", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"22", "full-text"=>"16", "pdf"=>"14", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"15", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"14", "full-text"=>"11", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"18", "full-text"=>"15", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"34", "full-text"=>"17", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"15", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"23", "full-text"=>"15", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"14", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"21", "full-text"=>"18", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"12", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"19", "full-text"=>"7", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
  • {"unique-ip"=>"21", "full-text"=>"13", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}
  • {"unique-ip"=>"22", "full-text"=>"18", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"10"}

Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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