Tipo
Artigos em Revista
Tipo de Documento
Artigo Completo
Título
CFTR processing, trafficking and interactions
Participantes na publicação
Margarida D. Amaral (Author)
Dep. Química e Bioquímica
BioISI
Darren M Hutt (Author)
Valeria Tomati (Author)
Hugo M. Botelho (Author)
Dep. Química e Bioquímica
BioISI
Nicoletta Pedemonte (Author)
Resumo
Mutations associated with cystic fibrosis (CF) have complex effects on the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common CF mutation, F508del, disrupts the processing to and stability at the plasma membrane and function as a Cl- channel. CFTR is surrounded by a dynamic network of interacting components, referred to as the CFTR Functional Landscape, that impact its synthesis, folding, stability, trafficking and function. CFTR interacting proteins can be manipulated by functional genomic approaches to rescue the trafficking and functional defects characteristic of CF. Here we review recent efforts to elucidate the impact of genetic variation on the ability of the nascent CFTR polypeptide to interact with the proteostatic environment. We also provide an overview of how specific components of this protein network can be modulated to rescue the trafficking and functional defects associated with the F508del variant of CFTR. The identification of novel proteins playing key roles in the processing of CFTR could pave the way for their use as novel therapeutic targets to provide synergistic correction of mutant CFTR for the greater benefit of individuals with CF.
Data de Submissão/Pedido
2019-07-23
Data de Aceitação
2019-10-15
Data de Publicação
2020-03
Suporte
Journal of Cystic Fibrosis
Identificadores da Publicação
ISSN - 1569-1993
Editora
Elsevier BV
Identificadores do Documento
DOI -
https://doi.org/10.1016/j.jcf.2019.10.017
URL -
http://dx.doi.org/10.1016/j.jcf.2019.10.017
Identificadores de Qualidade
SCIMAGO Q1 (2018) - 1.57 - Pulmonary and Respiratory Medicine
SCOPUS Q1 (2017) - 1.587 - Pulmonary and Respiratory Medicine
Web Of Science Q1 (2020) - 5.482 - RESPIRATORY SYSTEM - SCIE
SCIMAGO Q1 (2020) - 2.049 - Pediatrics, Perinatology and Child Health
SCIMAGO Q1 (2020) - 2.049 - Pulmonary and Respiratory Medicine
SCIMAGO Q1 (2019) - 1.411 - Pulmonary and Respiratory Medicine
Keywords
CFTR Cl-channel
F508del-CFTR
CFTR correctors
Proteostasis regulators
CFTR interactome
CFTR functional landscape
siRNA screening