The effect of the chemical chaperone 4-phenylbutyrate on secretion and activity of the p.Q160R missense variant of coagulation factor FVII.
Chemical chaperones
Endoplasmic reticulum
Factor VII deficiency
Mutations
Protein misfolding
Trafficking
Journal
Cell & bioscience
ISSN: 2045-3701
Titre abrégé: Cell Biosci
Pays: England
ID NLM: 101561195
Informations de publication
Date de publication:
2019
2019
Historique:
received:
18
02
2019
accepted:
17
08
2019
entrez:
31
8
2019
pubmed:
31
8
2019
medline:
31
8
2019
Statut:
epublish
Résumé
Congenital coagulation factor (F) VII deficiency is a rare bleeding disorder caused by mutations in the Through screening of compounds, we identified 4-phenylbutyrate (4-PBA) to increase the secretion of recombinant (r) FVII-160R by ~ 2.5-fold. Additionally, treatment with 4-PBA resulted in a modest increase in specific biological activity. Intracellular localization studies revealed that upon treatment with 4-PBA, rFVII-160R was secreted through Golgi and Golgi reassembly-stacking protein (GRASP)-structures. The present study demonstrates that the chemical chaperone 4-PBA, restores intracellular trafficking and increases the secretion of a missense FVII variant with functional properties in the extrinsic coagulation pathway.
Sections du résumé
BACKGROUND
BACKGROUND
Congenital coagulation factor (F) VII deficiency is a rare bleeding disorder caused by mutations in the
RESULTS
RESULTS
Through screening of compounds, we identified 4-phenylbutyrate (4-PBA) to increase the secretion of recombinant (r) FVII-160R by ~ 2.5-fold. Additionally, treatment with 4-PBA resulted in a modest increase in specific biological activity. Intracellular localization studies revealed that upon treatment with 4-PBA, rFVII-160R was secreted through Golgi and Golgi reassembly-stacking protein (GRASP)-structures.
CONCLUSIONS
CONCLUSIONS
The present study demonstrates that the chemical chaperone 4-PBA, restores intracellular trafficking and increases the secretion of a missense FVII variant with functional properties in the extrinsic coagulation pathway.
Identifiants
pubmed: 31467667
doi: 10.1186/s13578-019-0333-8
pii: 333
pmc: PMC6712599
doi:
Types de publication
Journal Article
Langues
eng
Pagination
69Déclaration de conflit d'intérêts
Competing interestsThe authors declare that they have no competing interests.
Références
EMBO J. 1999 Sep 15;18(18):4949-60
pubmed: 10487747
Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1796-801
pubmed: 10677536
Hum Mutat. 2001;17(1):3-17
pubmed: 11139238
Mol Ther. 2002 Jul;6(1):119-26
pubmed: 12095312
Br J Haematol. 2002 Sep;118(3):689-700
pubmed: 12181036
Biotechnol Bioeng. 2003 Jan 5;81(1):56-65
pubmed: 12432581
Pediatr Res. 2002 Dec;52(6):832-6
pubmed: 12438657
Nature. 2003 Dec 18;426(6968):905-9
pubmed: 14685252
Blood. 2004 Sep 1;104(5):1243-52
pubmed: 15138162
Oncol Rep. 2006 Feb;15(2):489-94
pubmed: 16391874
Biochem Biophys Res Commun. 2006 Mar 3;341(1):28-32
pubmed: 16406236
FEBS J. 2006 Apr;273(7):1331-49
pubmed: 16689923
Science. 2006 Aug 25;313(5790):1137-40
pubmed: 16931765
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18525-30
pubmed: 19011102
Anesth Analg. 2009 May;108(5):1447-52
pubmed: 19372318
Semin Thromb Hemost. 2009 Jun;35(4):400-6
pubmed: 19598068
Hepatology. 2009 Dec;50(6):1783-95
pubmed: 19937698
J Thromb Haemost. 2011 Apr;9(4):852-5
pubmed: 21595097
Cell. 2011 Sep 2;146(5):746-60
pubmed: 21884936
Thromb Res. 2012 Dec;130(6):948-55
pubmed: 22951415
PLoS One. 2012;7(9):e44505
pubmed: 22973456
Bioorg Med Chem Lett. 2013 Nov 1;23(21):6015-8
pubmed: 24044874
J Am Heart Assoc. 2013 Nov 15;2(6):e000440
pubmed: 24242684
Genet Mol Res. 2013 Dec 16;12(4):6813-24
pubmed: 24391029
Int J Biochem Cell Biol. 2015 Apr;61:45-52
pubmed: 25660369
BMC Biotechnol. 2015 Sep 18;15:87
pubmed: 26382581
Cell Biosci. 2015 Oct 09;5:57
pubmed: 26457178
Bioengineered. 2016 Apr;7(3):189-97
pubmed: 27116572
Rev Bras Hematol Hemoter. 2016 Apr-Jun;38(2):135-40
pubmed: 27208572
Biochim Biophys Acta Mol Basis Dis. 2018 Mar;1864(3):660-667
pubmed: 29246447
Thromb Haemost. 2018 Apr;118(4):664-675
pubmed: 29618153
J Thromb Haemost. 2018 Oct;16(10):2035-2043
pubmed: 29993188
Proc Natl Acad Sci U S A. 1986 Apr;83(8):2412-6
pubmed: 3486420
Cell. 1994 Jun 17;77(6):895-907
pubmed: 8004676
Cell. 1997 Oct 17;91(2):253-62
pubmed: 9346242
J Clin Invest. 1997 Nov 15;100(10):2457-65
pubmed: 9366560
J Biol Chem. 1998 Apr 3;273(14):8516-21
pubmed: 9525966
Thromb Haemost. 1998 Jun;79(6):1136-43
pubmed: 9657438
Anticancer Res. 1998 Jul-Aug;18(4A):2717-22
pubmed: 9703934
Blood. 1999 Feb 15;93(4):1237-44
pubmed: 9949166