Involvement of disulfide bond formation in the activation of heparanase

Siro Simizu, Takehiro Suzuki, Makoto Muroi, Shin Lai Ngit, Satoshi Takagi, Naoshi Dohmae, Hiroyuki Osada

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)7841-7849
Number of pages9
JournalCancer Research
Issue number16
Publication statusPublished - 2007 Aug 15
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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