Degradation of DNA topoisomerase I by a novel trypsin-like serine protease in proliferating human T lymphocytes

Hui Jye Chen, Ching Long Hwong, Cheng Hsu Wang, Jaulang Hwang

研究成果: 雜誌貢獻文章同行評審

11 引文 斯高帕斯(Scopus)

摘要

DNA topoisomerase I (Top I) contributes to various important biological functions, and its activity is therefore likely regulated in response to different physiological conditions. Increases in both the synthesis and degradation of Top I were previously shown to accompany phytohemagglutinin stimulation of proliferation in human peripheral T lymphocytes. The mechanism of this degradation of Top I has now been investigated with both in vivo and in vitro assays. The activity of a nuclear protease that specifically degrades Top I was induced in proliferating T lymphocytes. The full-length Top I protein (100 kDa) was sequentially degraded to 97- and 82-kDa fragments both in vivo and in vitro. The initial site of proteolytic cleavage was mapped to the NH2-terminal region of the enzyme. The degradation of Top I in vitro was inhibited by aprotinin or soybean trypsin inhibitor, suggesting that the enzyme responsible is a trypsin-like serine protease. Furthermore, Top I degradation by this protease was Mg2+-dependent. The Top I-specific protease activity induced during T lymphocytes proliferation was not detected in Jurkat (human T cell leukemia) cells and various other tested human cancer cell lines, possibly explaining why the abundance of Top I is increased in tumor cells.

原文英語
頁(從 - 到)13109-13117
頁數9
期刊Journal of Biological Chemistry
275
發行號17
DOIs
出版狀態已發佈 - 4月 28 2000
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 細胞生物學

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