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

被引:11
作者
Chen, HJ
Hwong, CL
Wang, CH
Hwang, JL [1 ]
机构
[1] Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan
[2] Natl Yang Ming Univ, Sch Life Sci, Inst Biochem, Taipei 112, Taiwan
[3] Chang Gung Mem Hosp, Dept Internal Med, Div Hematol Oncol, Taipei 105, Taiwan
关键词
D O I
10.1074/jbc.275.17.13109
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
DNA topoisomerase I (Topo 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 Topo I were previously shown to accompany phytohemagglutinin stimulation of proliferation in human peripheral T lymphocytes. The mechanism of this degradation of Topo I has now been investigated with both in vivo and in vitro assays. The activity of a nuclear protease that specifically degrades Topo I was induced in proliferating T lymphocytes. The full-length Topo 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 Topo I in vitro was inhibited by aprotinin or soybean trypsin inhibitor, suggesting that the enzyme responsible is a trypsin-like serine protease. Furthermore, Topo I degradation by this protease was Mg2+-dependent. The Topo 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 Topo I is increased in tumor cells.
引用
收藏
页码:13109 / 13117
页数:9
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