Evidence map›Paper›PMID 12361483›Full record

ArticleBMC biochemistry2002

The PEST sequence does not contribute to the stability of the cystic fibrosis transmembrane conductance regulator.

Eva Y Chen, David M Clarke

Abstract read
In one paragraph

Article in BMC biochemistry, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Eva Y ChenCanadian Institutes for Health Research Group in Membrane Biology, Department of Medicine, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. evayj.chen@utoronto.ca
David M Clarke

Funding

MDR1 MULTIDRUG TRANSPORTER--MECHANISM AND INHIBITIONR01CA080900 · NCI · UNIVERSITY OF TORONTO · PI CLARKE, DAVID M · 1999 to 2003
$530k
NCI NIH HHS R01 CA080900NCI NIH HHS R01-CA80900
6 · The paper itself

Abstract

backgroundEndoplasmic reticulum retention of misfolded cystic fibrosis transmembrane conductance regulator (CFTR) mutants and their rapid degradation is the major cause of cystic fibrosis (CF). An important goal is to understand the mechanism of how the misfolded proteins are recognized, retained, and targeted for degradation.

resultsUsing a web-based algorithm, PESTFind, we found a PEST sequence in the regulatory (R) domain of CFTR. The PEST sequence is found in many short-lived eukaryotic proteins and plays a role in their degradation. To determine its role in the stability and degradation of misprocessed CFTR, we introduced a number of site-directed mutations into the PEST sequence in the cDNA of DeltaF508 CFTR, the most prevalent misprocessed mutation found in CF patients. Analysis of these mutants showed that the disruption of the PEST sequence plays a minor role in the degradation of the CFTR mutants. Multiple mutations to the PEST sequence within the R domain of CFTR inhibit maturation of CFTR and prevent the formation of a 100 kDa degradation product. The mutations, however, do not improve the stability of the mutant DeltaF508 CFTR.

conclusionThese observations show that disruption of the structure of the R domain of CFTR can inhibit maturation of the protein and that the predicted PEST sequence plays no significant role in the degradation of CFTR.

Indexed as

Amino AcidsAmino Acid SequenceAnimalsCOS CellsCysteine EndopeptidasesCysteine Proteinase InhibitorsCystic Fibrosis Transmembrane Conductance RegulatorGlutamic AcidHumansLeupeptinsMolecular Sequence DataMultienzyme ComplexesMutationPlasmidsProlineProteasome Endopeptidase ComplexAmino Acidsbenzyloxycarbonylleucyl-leucyl-leucine aldehydeCFTR protein, humanCysteine EndopeptidasesCysteine Proteinase InhibitorsCystic Fibrosis Transmembrane Conductance RegulatorGlutamic AcidLeupeptinsMultienzyme ComplexesProlineProteasome Endopeptidase ComplexSerineThreonine

Identifiers

PMID12361483
PMCPMC130031

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.