Correction of F508del-CFTR Trafficking by the Sponge Alkaloid Latonduine Is Modulated by Interaction with PARP

被引：40

作者：

Carlile, Graeme W. ^{[1
]}

Keyzers, Robert A. ^{[3
,4
]}

Teske, Katrina A. ^{[1
]}

Robert, Renaud ^{[2
]}

Williams, David E. ^{[3
,4
]}

Linington, Roger G. ^{[3
,4
]}

Gray, Christopher A. ^{[3
,4
]}

Centko, Ryan M. ^{[3
,4
]}

Yan, Luping ^{[3
,4
]}

Anjos, Suzana M. ^{[1
]}

Sampson, Heidi M. ^{[1
]}

Zhang, Donglei ^{[1
]}

Liao, Jie ^{[2
]}

Hanrahan, John W. ^{[2
]}

Andersen, Raymond J. ^{[3
,4
]}

Thomas, David Y. ^{[1
]}

机构：

[1] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada

[2] McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada

[3] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada

[4] Univ British Columbia, Dept Earth & Ocean Sci, Vancouver, BC V6T 1Z1, Canada

来源：

CHEMISTRY & BIOLOGY | 2012年 / 19卷 / 10期

基金：

加拿大健康研究院; 加拿大创新基金会;

关键词：

TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS MUTATION; EPITHELIAL-CELLS; IN-VITRO; POLY(ADP-RIBOSE) POLYMERASES; INTRACELLULAR-TRANSPORT; CFTR; DEFECT; DELTA-F508; INHIBITOR;

D O I：

10.1016/j.chembiol.2012.08.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause CF. The most common mutation, F508 deletion, causes CFTR misfolding and endoplasmic reticulum retention, preventing it from trafficking to the cell surface. One approach to CF treatment is to identify compounds that correct the trafficking defect. We screened a marine extract collection and, after extract, deconvolution identified the latonduines as F508del-CFTR trafficking correctors that give functional correction in vivo. Using a biotinylated azido derivative of latonduine, we identified the poly(ADP-ribose) polymerase (PARP) family as latonduine target proteins. We show that latonduine binds to PARPs 1, 2, 3, 4, 5a, and 5b and inhibits PARP activity, especially PARP-3. Thus, latonduine corrects F508del-CFTR trafficking by modulating PARP activity. Latonduines represent pharmacologic agents for F508del-CFTR correction, and PARP-3 is a pathway for the development of CF treatments.

引用

页码：1288 / 1299

页数：12

共 40 条

[1] The Poly(ADP-ribose) polymerases (PARPs): New roles in intracellular transport [J].

Abd Elmageed, Zakaria Y. ;

Naura, Amarjit S. ;

Errami, Youssef ;

Zerfaoui, Mourad .

CELLULAR SIGNALLING, 2012, 24 (01) :1-8

[2]

Abdelkarim GE, 2001, INT J MOL MED, V7, P255

[3] Salivary secretion assay for drug efficacy for cystic fibrosis in mice [J].

Best, JA ;

Quinton, PM .

EXPERIMENTAL PHYSIOLOGY, 2005, 90 (02) :189-193

[4] Multiple 40-kDa heat-shock protein chaperones function in Tom70-dependent mitochondrial import [J].

Bhangoo, Melanie K. ;

Tzankov, Stefan ;

Fan, Anna C. Y. ;

Dejgaard, Kurt ;

Thomas, David Y. ;

Young, Jason C. .

MOLECULAR BIOLOGY OF THE CELL, 2007, 18 (09) :3414-3428

[5] Correctors of protein trafficking defects identified by a novel high-throughput screening assay [J].

Carlile, Graeme W. ;

Robert, Renaud ;

Zhang, Donglei ;

Teske, Katrina A. ;

Luo, Yishan ;

Hanrahan, John W. ;

Thomas, David Y. .

CHEMBIOCHEM, 2007, 8 (09) :1012-1020

[6] DEFECTIVE INTRACELLULAR-TRANSPORT AND PROCESSING OF CFTR IS THE MOLECULAR-BASIS OF MOST CYSTIC-FIBROSIS [J].

CHENG, SH ;

GREGORY, RJ ;

MARSHALL, J ;

PAUL, S ;

SOUZA, DW ;

WHITE, GA ;

ORIORDAN, CR ;

SMITH, AE .

CELL, 1990, 63 (04) :827-834

[7] Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation [J].

Clancy, J. P. ;

Rowe, Steven M. ;

Accurso, Frank J. ;

Aitken, Moira L. ;

Amin, Raouf S. ;

Ashlock, Melissa A. ;

Ballmann, Manfred ;

Boyle, Michael P. ;

Bronsveld, Inez ;

Campbell, Preston W. ;

De Boeck, Kris ;

Donaldson, Scott H. ;

Dorkin, Henry L. ;

Dunitz, Jordan M. ;

Durie, Peter R. ;

Jain, Manu ;

Leonard, Anissa ;

Mccoy, Karen S. ;

Moss, Richard B. ;

Pilewski, Joseph M. ;

Rosenbluth, Daniel B. ;

Rubenstein, Ronald C. ;

Schechter, Michael S. ;

Botfield, Martyn ;

Ordonez, Claudia L. ;

Spencer-Green, George T. ;

Vernillet, Laurent ;

Wisseh, Steve ;

Yen, Karl ;

Konstan, Michael W. .

THORAX, 2012, 67 (01) :12-18

[8] ALTERED CHLORIDE-ION CHANNEL KINETICS ASSOCIATED WITH THE DELTA-F508 CYSTIC-FIBROSIS MUTATION [J].

DALEMANS, W ;

BARBRY, P ;

CHAMPIGNY, G ;

JALLAT, S ;

DOTT, K ;

DREYER, D ;

CRYSTAL, RG ;

PAVIRANI, A ;

LECOCQ, JP ;

LAZDUNSKI, M .

NATURE, 1991, 354 (6354) :526-528

[9] LOCALIZATION OF CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR IN CHLORIDE SECRETORY EPITHELIA [J].

DENNING, GM ;

OSTEDGAARD, LS ;

CHENG, SH ;

SMITH, AE ;

WELSH, MJ .

JOURNAL OF CLINICAL INVESTIGATION, 1992, 89 (01) :339-349

[10] Sildenafil (Viagra) corrects ΔF508-CFTR location in nasal epithelial cells from patients with cystic fibrosis [J].

Dormer, RL ;

Harris, CM ;

Clark, Z ;

Pereira, MMC ;

Doull, IJM ;

Norez, C ;

Becq, F ;

McPherson, MA .

THORAX, 2005, 60 (01) :55-59

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