T cell mitogens induce increased DNA topoisomerase I protein levels and its translocation to the nucleus where activation of the enzyme occurs.
Induction of proliferation of human peripheral blood lymphocyte by T cell mitogens was found to be associated with dramatic increase in topoisomerase I DNA relaxing activity in the nuclear, but not in the cytosol, fraction. In addition, cell proliferation was associated with increased DNA topoisomerase I protein levels in both nuclear and cytosol fractions. Inhibitors of T cell proliferation abrogated both topoisomerase I protein levels and enzymatic activity. The results support a model in which cell proliferation is followed by increased DNA topoisomerase I protein levels and translocation of the enzymatically inactive molecule to the nucleus where additional regulatory mechanisms convert it into an active enzyme.
Gelkop
S
S
Department of Microbiology and Immunology, Ben Gurion University of the Negev, Beer Sheva, Israel.
Priel
E
E
Isakov
N
N
D000818:Animals; D001692:Biological Transport; D001773:Blood Cells / Q000502:physiology; D002451:Cell Compartmentation; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D015151:Immunoblotting; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D014018:Tissue Distribution
D008934:Mitogens; D004264:DNA Topoisomerases, Type I