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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)13109-13117
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number17
DOIs
Publication statusPublished - Apr 28 2000
Externally publishedYes

Fingerprint

Type I DNA Topoisomerase
T-cells
T-Lymphocytes
Degradation
Peptide Hydrolases
Cells
T-Cell Leukemia
trypsin-like serine protease
Aprotinin
Trypsin Inhibitors
Phytohemagglutinins
Enzymes
Soybeans
Tumors
Assays
Neoplasms
Cell Line

ASJC Scopus subject areas

  • Biochemistry

Cite this

Degradation of DNA topoisomerase I by a novel trypsin-like serine protease in proliferating human T lymphocytes. / Chen, Hui Jye; Hwong, Ching Long; Wang, Cheng Hsu; Hwang, Jaulang.

In: Journal of Biological Chemistry, Vol. 275, No. 17, 28.04.2000, p. 13109-13117.

Research output: Contribution to journalArticle

Chen, Hui Jye ; Hwong, Ching Long ; Wang, Cheng Hsu ; Hwang, Jaulang. / Degradation of DNA topoisomerase I by a novel trypsin-like serine protease in proliferating human T lymphocytes. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 17. pp. 13109-13117.
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