Involvement of disulfide bond formation in the activation of heparanase.

Abstract:

:Heparanase is overexpressed in many solid tumor cells and is capable of specifically cleaving heparan sulfate, and this activity is associated with the metastatic potential of tumor cells; however, the activation mechanism of heparanase has remained unknown. In this study, we investigated the link between disulfide bond formation and the activation of heparanase in human tumor cells. Mass spectrometry analysis of heparanase purified from a conditioned medium of human fibrosarcoma cells revealed two disulfide bonds, Cys127-Cys179 and Cys437-Cys542, and one S-cysteinylation at the Cys211 residue. It was shown that, although the formation of the Cys127-Cys179 bond and S-cysteinylation at Cys211 have little effect on heparanase function, the disulfide bond between Cys437 and Cys542 is necessary for the secretion and activation of heparanase. Thus, the present findings will provide a basis for the further refinement of heparanase structural studies and for the development of novel heparanase inhibitors.

journal_name

Cancer Res

journal_title

Cancer research

authors

Simizu S,Suzuki T,Muroi M,Lai NS,Takagi S,Dohmae N,Osada H

doi

10.1158/0008-5472.CAN-07-1053

subject

Has Abstract

pub_date

2007-08-15 00:00:00

pages

7841-9

issue

16

eissn

0008-5472

issn

1538-7445

pii

67/16/7841

journal_volume

67

pub_type

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