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Article ; Online: Distinct proteostasis states drive pharmacologic chaperone susceptibility for cystic fibrosis transmembrane conductance regulator misfolding mutants.

McDonald, Eli Fritz / Sabusap, Carleen Mae P / Kim, Minsoo / Plate, Lars

2022 Volume 33, Issue 7, Page(s) ar62

Abstract: Pharmacological chaperones represent a class of therapeutic compounds for treating protein misfolding diseases. One of the most prominent examples is the FDA-approved pharmacological chaperone lumacaftor (VX-809), which has transformed cystic fibrosis ( ... ...

Abstract	Pharmacological chaperones represent a class of therapeutic compounds for treating protein misfolding diseases. One of the most prominent examples is the FDA-approved pharmacological chaperone lumacaftor (VX-809), which has transformed cystic fibrosis (CF) therapy. CF is a fatal disease caused by mutations in the CF transmembrane conductance regulator (CFTR). VX-809 corrects folding of F508del CFTR, the most common patient mutation, yet F508del exhibits only mild VX-809 response. In contrast, rarer mutations P67L and L206W are
MeSH term(s)	Aminopyridines/pharmacology ; Aminopyridines/therapeutic use ; Benzodioxoles/pharmacology ; Benzodioxoles/therapeutic use ; Cystic Fibrosis/drug therapy ; Cystic Fibrosis/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Humans ; Mutation/genetics ; Proteostasis ; Signal Transduction
Chemical Substances	Aminopyridines ; Benzodioxoles ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
Language	English
Publishing date	2022-04-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1098979-1
ISSN	1939-4586 ; 1059-1524
ISSN (online)	1939-4586
ISSN	1059-1524
DOI	10.1091/mbc.E21-11-0578
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Article: Elexacaftor/VX-445-mediated CFTR interactome remodeling reveals differential correction driven by mutation-specific translational dynamics.

Kim, Minsoo / McDonald, Eli Fritz / Sabusap, Carleen Mae P / Timalsina, Bibek / Joshi, Disha / Hong, Jeong S / Rab, Andras / Sorscher, Eric J / Plate, Lars

bioRxiv : the preprint server for biology

2023

Abstract: Cystic fibrosis (CF) is one of the most prevalent lethal genetic diseases with over 2000 identified mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Pharmacological chaperones such as Lumacaftor (VX-809), Tezacaftor (VX- ... ...

Abstract	Cystic fibrosis (CF) is one of the most prevalent lethal genetic diseases with over 2000 identified mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Pharmacological chaperones such as Lumacaftor (VX-809), Tezacaftor (VX-661) and Elexacaftor (VX-445) treat mutation-induced defects by stabilizing CFTR and are called correctors. These correctors improve proper folding and thus facilitate processing and trafficking to increase the amount of functional CFTR on the cell surface. Yet, CFTR variants display differential responses to each corrector. Here, we report variants P67L and L206W respond similarly to VX-809 but divergently to VX-445 with P67L exhibiting little rescue when treated with VX-445. We investigate the underlying cellular mechanisms of how CFTR biogenesis is altered by correctors in these variants. Affinity purification-mass spectrometry (AP-MS) multiplexed with isobaric Tandem Mass Tags (TMT) was used to quantify CFTR protein-protein interaction changes between variants P67L and L206W. VX-445 facilitates unique proteostasis factor interactions especially in translation, folding, and degradation pathways in a CFTR variant-dependent manner. A number of these interacting proteins knocked down by siRNA, such as ribosomal subunit proteins, moderately rescued fully glycosylated P67L. Importantly, these knock-downs sensitize P67L to VX-445 and further enhance the correction of this variant. Our results provide a better understanding of VX-445 biological mechanism of action and reveal cellular targets that may sensitize unresponsive CFTR variants to known and available correctors.
Language	English
Publishing date	2023-02-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.04.527134
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Article ; Online: Elexacaftor/VX-445-mediated CFTR interactome remodeling reveals differential correction driven by mutation-specific translational dynamics.

Kim, Minsoo / McDonald, Eli Fritz / Sabusap, Carleen Mae P / Timalsina, Bibek / Joshi, Disha / Hong, Jeong S / Rab, Andras / Sorscher, Eric J / Plate, Lars

The Journal of biological chemistry

2023 Volume 299, Issue 10, Page(s) 105242

Abstract	Cystic fibrosis (CF) is one of the most prevalent lethal genetic diseases with over 2000 identified mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Pharmacological chaperones such as lumacaftor (VX-809), tezacaftor (VX-661), and elexacaftor (VX-445) treat mutation-induced defects by stabilizing CFTR and are called correctors. These correctors improve proper folding and thus facilitate processing and trafficking to increase the amount of functional CFTR on the cell surface. Yet, CFTR variants display differential responses to each corrector. Here, we report that variants P67L and L206W respond similarly to VX-809 but divergently to VX-445 with P67L exhibiting little rescue when treated with VX-445. We investigate the underlying cellular mechanisms of how CFTR biogenesis is altered by correctors in these variants. Affinity purification-mass spectrometry multiplexed with isobaric tandem mass tags was used to quantify CFTR protein-protein interaction changes between variants P67L and L206W. VX-445 facilitates unique proteostasis factor interactions especially in translation, folding, and degradation pathways in a CFTR variant-dependent manner. A number of these interacting proteins knocked down by siRNA, such as ribosomal subunit proteins, moderately rescued fully glycosylated P67L. Importantly, these knockdowns sensitize P67L to VX-445 and further enhance the trafficking correction of this variant. Partial inhibition of protein translation also mildly sensitizes P67L CFTR to VX-445 correction, supporting a role for translational dynamics in the rescue mechanism of VX-445. Our results provide a better understanding of VX-445 biological mechanism of action and reveal cellular targets that may sensitize nonresponsive CFTR variants to known and available correctors.
MeSH term(s)	Humans ; Benzodioxoles/pharmacology ; Cystic Fibrosis/genetics ; Cystic Fibrosis/physiopathology ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Gene Knockdown Techniques ; Genetic Variation ; HEK293 Cells ; Mutation ; Protein Biosynthesis/genetics ; Proteostasis/drug effects ; Pyrazoles/pharmacology ; Ribosomal Proteins/genetics
Chemical Substances	Benzodioxoles ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; elexacaftor (RRN67GMB0V) ; lumacaftor (EGP8L81APK) ; Pyrazoles ; Ribosomal Proteins
Language	English
Publishing date	2023-09-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2023.105242
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Article ; Online: The CFTR P67L variant reveals a key role for N-terminal lasso helices in channel folding, maturation, and pharmacologic rescue.

Sabusap, Carleen Mae / Joshi, Disha / Simhaev, Luba / Oliver, Kathryn E / Senderowitz, Hanoch / van Willigen, Marcel / Braakman, Ineke / Rab, Andras / Sorscher, Eric J / Hong, Jeong S

The Journal of biological chemistry

2021 Volume 296, Page(s) 100598

Abstract: Patients with cystic fibrosis (CF) harboring the P67L variant in the cystic fibrosis transmembrane conductance regulator (CFTR) often exhibit a typical CF phenotype, including severe respiratory compromise. This rare mutation (reported in <300 patients ... ...

Abstract	Patients with cystic fibrosis (CF) harboring the P67L variant in the cystic fibrosis transmembrane conductance regulator (CFTR) often exhibit a typical CF phenotype, including severe respiratory compromise. This rare mutation (reported in <300 patients worldwide) responds robustly to CFTR correctors, such as lumacaftor and tezacaftor, with rescue in model systems that far exceed what can be achieved for the archetypical CFTR mutant F508del. However, the specific molecular consequences of the P67L mutation are poorly characterized. In this study, we conducted biochemical measurements following low-temperature growth and/or intragenic suppression, which suggest a mechanism underlying P67L that (1) shares key pathogenic features with F508del, including off-pathway (non-native) folding intermediates, (2) is linked to folding stability of nucleotide-binding domains 1 and 2, and (3) demonstrates pharmacologic rescue that requires domains in the carboxyl half of the protein. We also investigated the "lasso" helices 1 and 2, which occur immediately upstream of P67. Based on limited proteolysis, pulse chase, and molecular dynamics analysis of full-length CFTR and a series of deletion constructs, we argue that P67L and other maturational processing (class 2) defects impair the integrity of the lasso motif and confer misfolding of downstream domains. Thus, amino-terminal missense variants elicit a conformational change throughout CFTR that abrogates maturation while providing a robust substrate for pharmacologic repair.
MeSH term(s)	Cell Line ; Cystic Fibrosis Transmembrane Conductance Regulator/chemistry ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Humans ; Molecular Dynamics Simulation ; Mutation ; Protein Conformation, alpha-Helical ; Protein Folding
Chemical Substances	Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
Language	English
Publishing date	2021-03-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2021.100598
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Article: A Comparison between Two Pathophysiologically Different yet Microbiologically Similar Lung Diseases: Cystic Fibrosis and Chronic Obstructive Pulmonary Disease.

Fenker, Daniel E / McDaniel, Cameron T / Panmanee, Warunya / Panos, Ralph J / Sorscher, Eric J / Sabusap, Carleen / Clancy, John P / Hassett, Daniel J

International journal of respiratory and pulmonary medicine

2018 Volume 5, Issue 2

Abstract: Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are chronic pulmonary diseases that affect ~70,000 and 251 million individuals worldwide, respectively. Although these two diseases have distinctly different pathophysiologies, both ... ...

Abstract	Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are chronic pulmonary diseases that affect ~70,000 and 251 million individuals worldwide, respectively. Although these two diseases have distinctly different pathophysiologies, both cause chronic respiratory insufficiency that erodes quality of life and causes significant morbidity and eventually death. In both CF and COPD, the respiratory microbiome plays a major contributing role in disease progression and morbidity. Pulmonary pathogens can differ dramatically during various stages of each disease and frequently cause acute worsening of lung function due to disease exacerbation. Despite some similarities, outcome and timing/type of exacerbation can also be quite different between CF and COPD. Given these clinical distinctions, both patients and physicians should be aware of emerging therapeutic options currently being offered or in development for the treatment of lung infections in individuals with CF and COPD. Although interventions are available that prolong life and mitigate morbidity, neither disorder is curable. Both acute and chronic pulmonary infections contribute to an inexorable downward course and may trigger exacerbations, culminating in loss of lung function or respiratory failure. Knowledge of the pulmonary pathogens causing these infections, their clinical presentation, consequences, and management are, therefore, critical. In this review, we compare and contrast CF and COPD, including underlying causes, general outcomes, features of the lung microbiome, and potential treatment strategies.
Language	English
Publishing date	2018-11-29
Publishing country	United States
Document type	Journal Article
ISSN	2378-3516
ISSN	2378-3516
DOI	10.23937/2378-3516/1410098
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Article ; Online: Thromboxane-Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis.

American journal of respiratory and critical care medicine

2022 Volume 206, Issue 5, Page(s) 596–607

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Animals ; Bleomycin/pharmacology ; F2-Isoprostanes/metabolism ; Fibroblasts/metabolism ; Humans ; Idiopathic Pulmonary Fibrosis/genetics ; Lung/metabolism ; Mice ; Mice, Inbred C57BL ; Prostaglandins/metabolism ; Receptors, Thromboxane/metabolism ; Thromboxanes/metabolism ; Transforming Growth Factor beta/metabolism
Chemical Substances	F2-Isoprostanes ; Prostaglandins ; Receptors, Thromboxane ; Thromboxanes ; Transforming Growth Factor beta ; Bleomycin (11056-06-7)
Language	English
Publishing date	2022-06-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202106-1503OC
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Article ; Online: The unfolded protein response transcription factor XBP1s ameliorates Alzheimer's disease by improving synaptic function and proteostasis.

Duran-Aniotz, Claudia / Poblete, Natalia / Rivera-Krstulovic, Catalina / Ardiles, Álvaro O / Díaz-Hung, Mei Li / Tamburini, Giovanni / Sabusap, Carleen Mae P / Gerakis, Yannis / Cabral-Miranda, Felipe / Diaz, Javier / Fuentealba, Matias / Arriagada, Diego / Muñoz, Ernesto / Espinoza, Sandra / Martinez, Gabriela / Quiroz, Gabriel / Sardi, Pablo / Medinas, Danilo B / Contreras, Darwin /

Piña, Ricardo / Lourenco, Mychael V / Ribeiro, Felipe C / Ferreira, Sergio T / Rozas, Carlos / Morales, Bernardo / Plate, Lars / Gonzalez-Billault, Christian / Palacios, Adrian G / Hetz, Claudio

Molecular therapy : the journal of the American Society of Gene Therapy

2023 Volume 31, Issue 7, Page(s) 2240–2256

Abstract: Alteration in the buffering capacity of the proteostasis network is an emerging feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is the main adaptive pathway to ... ...

Abstract	Alteration in the buffering capacity of the proteostasis network is an emerging feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is the main adaptive pathway to cope with protein folding stress at the ER. Inositol-requiring enzyme-1 (IRE1) operates as a central ER stress sensor, enabling the establishment of adaptive and repair programs through the control of the expression of the transcription factor X-box binding protein 1 (XBP1). To artificially enforce the adaptive capacity of the UPR in the AD brain, we developed strategies to express the active form of XBP1 in the brain. Overexpression of XBP1 in the nervous system using transgenic mice reduced the load of amyloid deposits and preserved synaptic and cognitive function. Moreover, local delivery of XBP1 into the hippocampus of an 5xFAD mice using adeno-associated vectors improved different AD features. XBP1 expression corrected a large proportion of the proteomic alterations observed in the AD model, restoring the levels of several synaptic proteins and factors involved in actin cytoskeleton regulation and axonal growth. Our results illustrate the therapeutic potential of targeting UPR-dependent gene expression programs as a strategy to ameliorate AD features and sustain synaptic function.
MeSH term(s)	Animals ; Mice ; Alzheimer Disease/genetics ; Alzheimer Disease/therapy ; Alzheimer Disease/metabolism ; Endoplasmic Reticulum Stress/genetics ; Mice, Transgenic ; Proteomics ; Proteostasis/genetics ; Signal Transduction/physiology ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Unfolded Protein Response/genetics
Chemical Substances	Transcription Factors ; Xbp1 protein, mouse
Language	English
Publishing date	2023-04-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2023.03.028
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Article ; Online: The Genetic Landscape of Familial Pulmonary Fibrosis.

Liu, Qi / Zhou, Yuan / Cogan, Joy D / Mitchell, Daphne B / Sheng, Quanhu / Zhao, Shilin / Bai, Youhuang / Ciombor, Kristen K / Sabusap, Carleen M / Malabanan, M Merced / Markin, Cheryl R / Douglas, Katrina / Ding, Guixiao / Banovich, Nicholas E / Nickerson, Deborah A / Blue, Elizabeth E / Bamshad, Michael J / Brown, Kevin K / Schwartz, David A /

Phillips, John A / Martinez-Barricarte, Ruben / Salisbury, Margaret L / Shyr, Yu / Loyd, James E / Kropski, Jonathan A / Blackwell, Timothy S

American journal of respiratory and critical care medicine

2023 Volume 207, Issue 10, Page(s) 1345–1357

Abstract: Rationale and Objectives: ...

Abstract	Rationale and Objectives:
MeSH term(s)	Humans ; Pulmonary Fibrosis/genetics ; Endothelial Cells ; Lung Diseases, Interstitial/genetics ; Risk Factors ; Telomere ; Genetic Predisposition to Disease/genetics ; Receptors, Lysophosphatidic Acid/genetics
Chemical Substances	GPR87 protein, human ; Receptors, Lysophosphatidic Acid
Language	English
Publishing date	2023-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202204-0781OC
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Article ; Online: Unfolded protein response IRE1/XBP1 signaling is required for healthy mammalian brain aging.

Cabral-Miranda, Felipe / Tamburini, Giovanni / Martinez, Gabriela / Ardiles, Alvaro O / Medinas, Danilo B / Gerakis, Yannis / Hung, Mei-Li Diaz / Vidal, René / Fuentealba, Matias / Miedema, Tim / Duran-Aniotz, Claudia / Diaz, Javier / Ibaceta-Gonzalez, Cristobal / Sabusap, Carleen M / Bermedo-Garcia, Francisca / Mujica, Paula / Adamson, Stuart / Vitangcol, Kaitlyn / Huerta, Hernan /

Zhang, Xu / Nakamura, Tomohiro / Sardi, Sergio Pablo / Lipton, Stuart A / Kennedy, Brian K / Henriquez, Juan Pablo / Cárdenas, J Cesar / Plate, Lars / Palacios, Adrian G / Hetz, Claudio

The EMBO journal

2022 Volume 41, Issue 22, Page(s) e111952

Abstract: Aging is a major risk factor to develop neurodegenerative diseases and is associated with decreased buffering capacity of the proteostasis network. We investigated the significance of the unfolded protein response (UPR), a major signaling pathway ... ...

Abstract	Aging is a major risk factor to develop neurodegenerative diseases and is associated with decreased buffering capacity of the proteostasis network. We investigated the significance of the unfolded protein response (UPR), a major signaling pathway activated to cope with endoplasmic reticulum (ER) stress, in the functional deterioration of the mammalian brain during aging. We report that genetic disruption of the ER stress sensor IRE1 accelerated age-related cognitive decline. In mouse models, overexpressing an active form of the UPR transcription factor XBP1 restored synaptic and cognitive function, in addition to reducing cell senescence. Proteomic profiling of hippocampal tissue showed that XBP1 expression significantly restore changes associated with aging, including factors involved in synaptic function and pathways linked to neurodegenerative diseases. The genes modified by XBP1 in the aged hippocampus where also altered. Collectively, our results demonstrate that strategies to manipulate the UPR in mammals may help sustain healthy brain aging.
MeSH term(s)	Animals ; Mice ; Aging/genetics ; Brain/metabolism ; Endoplasmic Reticulum Stress/genetics ; Protein Serine-Threonine Kinases/genetics ; Proteomics ; Signal Transduction/physiology ; Unfolded Protein Response ; X-Box Binding Protein 1/genetics ; X-Box Binding Protein 1/metabolism
Chemical Substances	Protein Serine-Threonine Kinases (EC 2.7.11.1) ; X-Box Binding Protein 1 ; Ern2 protein, mouse (EC 2.7.1.-) ; Xbp1 protein, mouse
Language	English
Publishing date	2022-10-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.15252/embj.2022111952
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Article ; Online: Slowing ribosome velocity restores folding and function of mutant CFTR.

Oliver, Kathryn E / Rauscher, Robert / Mijnders, Marjolein / Wang, Wei / Wolpert, Matthew J / Maya, Jessica / Sabusap, Carleen M / Kesterson, Robert A / Kirk, Kevin L / Rab, Andras / Braakman, Ineke / Hong, Jeong S / Hartman, John L / Ignatova, Zoya / Sorscher, Eric J

The Journal of clinical investigation

2019 Volume 129, Issue 12, Page(s) 5236–5253

Abstract: Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), with approximately 90% of patients harboring at least one copy of the disease-associated variant F508del. We utilized a yeast phenomic system to identify ... ...

Abstract	Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), with approximately 90% of patients harboring at least one copy of the disease-associated variant F508del. We utilized a yeast phenomic system to identify genetic modifiers of F508del-CFTR biogenesis, from which ribosomal protein L12 (RPL12/uL11) emerged as a molecular target. In the present study, we investigated mechanism(s) by which suppression of RPL12 rescues F508del protein synthesis and activity. Using ribosome profiling, we found that rates of translation initiation and elongation were markedly slowed by RPL12 silencing. However, proteolytic stability and patch-clamp assays revealed RPL12 depletion significantly increased F508del-CFTR steady-state expression, interdomain assembly, and baseline open-channel probability. We next evaluated whether Rpl12-corrected F508del-CFTR could be further enhanced with concomitant pharmacologic repair (e.g., using clinically approved modulators lumacaftor and tezacaftor) and demonstrated additivity of these treatments. Rpl12 knockdown also partially restored maturation of specific CFTR variants in addition to F508del, and WT Cftr biogenesis was enhanced in the pancreas, colon, and ileum of Rpl12 haplosufficient mice. Modulation of ribosome velocity therefore represents a robust method for understanding both CF pathogenesis and therapeutic response.
MeSH term(s)	Aminopyridines/pharmacology ; Animals ; Benzodioxoles/pharmacology ; Bronchi/metabolism ; Colon/metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/chemistry ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Epithelium/metabolism ; Female ; Gene Silencing ; HEK293 Cells ; Humans ; Ileum/metabolism ; Indoles/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutant Proteins/chemistry ; Mutant Proteins/genetics ; Mutation ; Pancreas/metabolism ; Patch-Clamp Techniques ; Protein Conformation ; Protein Folding ; Rats ; Ribosomal Proteins/metabolism ; Ribosomes/metabolism
Chemical Substances	Aminopyridines ; Benzodioxoles ; Cftr protein, mouse ; Indoles ; Mutant Proteins ; RPL12 protein, human ; Ribosomal Proteins ; Rpl12 protein, mouse ; cystic fibrosis transmembrane conductance regulator delta F508 ; tezacaftor ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; lumacaftor (EGP8L81APK)
Language	English
Publishing date	2019-11-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI124282
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