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CFTR mutations altering CFTR fragmentation

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CFTR mutations altering CFTR fragmentation. / Tosoni, Kendra; Stobbart, Michelle; Cassidy, Diane M; Venerando, Andrea; Pagano, Mario A; Luz, Simao; Amaral, Margarida D; Kunzelmann, Karl; Pinna, Lorenzo A; Farinha, Carlos Miguel; Mehta, Anil (Lead / Corresponding author).

In: Biochemical Journal, Vol. 449, No. 1, 2013, p. 295-305.

Research output: Contribution to journalArticle

Harvard

Tosoni, K, Stobbart, M, Cassidy, DM, Venerando, A, Pagano, MA, Luz, S, Amaral, MD, Kunzelmann, K, Pinna, LA, Farinha, CM & Mehta, A 2013, 'CFTR mutations altering CFTR fragmentation' Biochemical Journal, vol 449, no. 1, pp. 295-305., 10.1042/BJ20121240

APA

Tosoni, K., Stobbart, M., Cassidy, D. M., Venerando, A., Pagano, M. A., Luz, S., ... Mehta, A. (2013). CFTR mutations altering CFTR fragmentation. Biochemical Journal, 449(1), 295-305. 10.1042/BJ20121240

Vancouver

Tosoni K, Stobbart M, Cassidy DM, Venerando A, Pagano MA, Luz S et al. CFTR mutations altering CFTR fragmentation. Biochemical Journal. 2013;449(1):295-305. Available from: 10.1042/BJ20121240

Author

Tosoni, Kendra; Stobbart, Michelle; Cassidy, Diane M; Venerando, Andrea; Pagano, Mario A; Luz, Simao; Amaral, Margarida D; Kunzelmann, Karl; Pinna, Lorenzo A; Farinha, Carlos Miguel; Mehta, Anil (Lead / Corresponding author) / CFTR mutations altering CFTR fragmentation.

In: Biochemical Journal, Vol. 449, No. 1, 2013, p. 295-305.

Research output: Contribution to journalArticle

Bibtex - Download

@article{e414c6e8432849fbb5fa35a78474b243,
title = "CFTR mutations altering CFTR fragmentation",
author = "Kendra Tosoni and Michelle Stobbart and Cassidy, {Diane M} and Andrea Venerando and Pagano, {Mario A} and Simao Luz and Amaral, {Margarida D} and Karl Kunzelmann and Pinna, {Lorenzo A} and Farinha, {Carlos Miguel} and Anil Mehta",
year = "2013",
doi = "10.1042/BJ20121240",
volume = "449",
number = "1",
pages = "295--305",
journal = "Biochemical Journal",
issn = "0264-6021",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - CFTR mutations altering CFTR fragmentation

A1 - Tosoni,Kendra

A1 - Stobbart,Michelle

A1 - Cassidy,Diane M

A1 - Venerando,Andrea

A1 - Pagano,Mario A

A1 - Luz,Simao

A1 - Amaral,Margarida D

A1 - Kunzelmann,Karl

A1 - Pinna,Lorenzo A

A1 - Farinha,Carlos Miguel

A1 - Mehta,Anil

AU - Tosoni,Kendra

AU - Stobbart,Michelle

AU - Cassidy,Diane M

AU - Venerando,Andrea

AU - Pagano,Mario A

AU - Luz,Simao

AU - Amaral,Margarida D

AU - Kunzelmann,Karl

AU - Pinna,Lorenzo A

AU - Farinha,Carlos Miguel

AU - Mehta,Anil

PY - 2013

Y1 - 2013

N2 - Most cystic fibrosis (CF), results from deletion of a phenylalanine (F508) in the CF transmembrane-conductance regulator (CFTR, ABCC7) which causes ER-degradation of the mutant. Using stably CFTR-expressing BHK cell lines, we demonstrate that wild type- and F508delCFTR are cleaved into differently sized, N- and C-terminal bearing fragments, with each hemi-CFTR carrying its nearest nucleotide binding domain (NBD), reflecting differential cleavage through the central CFTR R-domain. Similar NBD1-bearing fragments are present in the natively expressing HBE epithelial cell line. We also observe multiple smaller fragments of different sizes in BHK cells, particularly after F508del-mutation (ladder pattern). Trapping wild type CFTR in the ER did not generate a F508del fragmentation fingerprint. Fragments change their size/pattern again post mutation at sites involved in CFTR's in vitro interaction with the pleiotropic protein kinase CK2 (S511A in NBD1). F508del- and S511A- mutation generate different fragmentation fingerprints that are each unlike wild type; yet both mutants generate a new N-terminal-bearing CFTR fragments that are not observed with other CK2-related mutations (S511D, S422A/D, T1471A/D). We conclude that F508delCFTR is not degraded completely and there exists a relationship between CFTR's fragmentation fingerprint and the CFTR sequence through putative CK2-interactive sites that lie near F508.

AB - Most cystic fibrosis (CF), results from deletion of a phenylalanine (F508) in the CF transmembrane-conductance regulator (CFTR, ABCC7) which causes ER-degradation of the mutant. Using stably CFTR-expressing BHK cell lines, we demonstrate that wild type- and F508delCFTR are cleaved into differently sized, N- and C-terminal bearing fragments, with each hemi-CFTR carrying its nearest nucleotide binding domain (NBD), reflecting differential cleavage through the central CFTR R-domain. Similar NBD1-bearing fragments are present in the natively expressing HBE epithelial cell line. We also observe multiple smaller fragments of different sizes in BHK cells, particularly after F508del-mutation (ladder pattern). Trapping wild type CFTR in the ER did not generate a F508del fragmentation fingerprint. Fragments change their size/pattern again post mutation at sites involved in CFTR's in vitro interaction with the pleiotropic protein kinase CK2 (S511A in NBD1). F508del- and S511A- mutation generate different fragmentation fingerprints that are each unlike wild type; yet both mutants generate a new N-terminal-bearing CFTR fragments that are not observed with other CK2-related mutations (S511D, S422A/D, T1471A/D). We conclude that F508delCFTR is not degraded completely and there exists a relationship between CFTR's fragmentation fingerprint and the CFTR sequence through putative CK2-interactive sites that lie near F508.

UR - http://www.scopus.com/inward/record.url?scp=84870934566&partnerID=8YFLogxK

U2 - 10.1042/BJ20121240

DO - 10.1042/BJ20121240

M1 - Article

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 1

VL - 449

SP - 295

EP - 305

ER -

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