View : 18 Download: 0

The presence of outer arm fucose residues on the N -glycans of tissue inhibitor of metalloproteinases-1 reduces its activity

Title
The presence of outer arm fucose residues on the N -glycans of tissue inhibitor of metalloproteinases-1 reduces its activity
Authors
Kim H.I.Saldova R.Park J.H.Lee Y.H.Harvey D.J.Wormald M.R.Wynne K.Elia G.Kim H.-J.Rudd P.M.Lee S.-T.
Ewha Authors
김화정
SCOPUS Author ID
김화정scopus
Issue Date
2013
Journal Title
Journal of Proteome Research
ISSN
1535-3893JCR Link
Citation
vol. 12, no. 8, pp. 3547 - 3560
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Tissue inhibitor of metalloproteinases-1 (TIMP-1) inhibits matrix metalloproteinases (MMPs) by binding at a 1:1 stoichiometry. Here we have shown the involvement of N-glycosylation in the MMP inhibitory ability of TIMP-1. TIMP-1, purified from HEK 293 cells overexpressing TIMP-1 (293 TIMP-1), showed less binding and inhibitory abilities to MMPs than TIMP-1 purified from fibroblasts or SF9 insect cells infected with TIMP-1 baculovirus. Following deglycosylation of TIMP-1, all forms of TIMP-1 showed similar levels of MMP binding and inhibition, suggesting that glycosylation is involved in the regulation of these TIMP-1 activities. Analysis of the N-glycan structures showed that SF9 TIMP-1 has the simplest N-glycan structures, followed by fibroblast TIMP-1 and 293 TIMP-1, in order of increasing complexity in their N-glycan structures. Further analyses showed that cleavage of outer arm fucose residues from the N-glycans of 293 TIMP-1 or knockdown of both FUT4 and FUT7 (which encode for fucosyltransferases that add outer arm fucose residues to N-glycans) enhanced the MMP-binding and catalytic abilities of 293 TIMP-1, bringing them up to the levels of the other TIMP-1. These results demonstrate that the ability of TIMP-1 to inhibit MMPs is at least in part regulated by outer arm fucosylation of its N-glycans. © 2013 American Chemical Society.
DOI
10.1021/pr400276r
Appears in Collections:
약학대학 > 약학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE