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

研究成果: Article査読

45 被引用数 (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.

ジャーナルCancer Research
出版ステータスPublished - 2007 8月 15

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究


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