Benzo(c)quinolizinium drugs inhibit degradation of Delta F508-CFTR cytoplasmic domain

Stratford, Fiona L. L., Pereira, Malcolm Martin Claude, Becq, Frederic, McPherson, Margaret A. and Dormer, Robert Leslie 2003. Benzo(c)quinolizinium drugs inhibit degradation of Delta F508-CFTR cytoplasmic domain. Biochemical and Biophysical Research Communications 300 (2) , pp. 524-30. 10.1016/S0006-291X(02)02883-8

Full text not available from this repository.

Abstract

Proteins comprising the first nucleotide-binding- and R-domains of wild-type and ?F508 cystic fibrosis transmembrane conductance regulator (CFTR) have been synthesised by in vitro transcription/translation. The kinetics and extent of degradation of wild-type and ?F508 cytoplasmic domain proteins in rabbit reticulocyte lysates, in which proteasome activity was inhibited, were similar, with a half-life of approximately 4 h. The results show for the first time, that the benzo(c)quinolizinium compounds, MPB-07 and MPB-91, selectively inhibit degradation of the ?F508 cytoplasmic domain protein. Studies using protease inhibitors demonstrated that both ?F508 and wild-type proteins are substrates for cysteine proteases. The studies provide evidence that benzo(c)quinolizinium compounds protect a proteolytic cleavage site by direct binding to the first cytoplasmic domain of ?F508-CFTR and this is a likely mechanism for increasing ?F508-CFTR trafficking in intact cells.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QR Microbiology R Medicine > R Medicine (General)
Uncontrolled Keywords:	Cystic fibrosis transmembrane conductance regulator protein; Cytoplasmic domain; ?F508 mutation; Degradation; Cysteine protease; Benzo(c)quinolizinium compounds
ISSN:	1090-2104
Last Modified:	18 Oct 2017 08:24
URI:	https://orca.cardiff.ac.uk/id/eprint/440

Actions (repository staff only)

Edit Item