Induction of DNA synthesis in isolated nuclei by cytoplasmic factors: inhibition by protease inhibitors.
Wong, R L
Cytoplasmic extracts from spontaneously proliferating and mitogen-activated lymphoid cells contain a protein factor called ADR (activator of DNA replication) that induces DNA synthesis in isolated quiescent nuclei. ADR-containing preparations have proteolytic activity, as indicated by their ability to degrade fibrin in a plasminogen-independent and plasminogen-dependent manner. In addition, aprotinin, a nonspecific protease inhibitor, abrogates ADR-induced DNA synthesis in a dose-dependent fashion. Preincubation studies demonstrated that the effect of aprotinin is not due to its suppressive effects on the nuclei themselves. Other protease inhibitors such as leupeptin, p-aminobenzamidine, and N-alpha-tosyllysine chloromethyl ketone are also inhibitory, but soybean trypsin inhibitor is without effect. ADR activity can be removed from active extracts by adsorption with aprotinin-conjugated agarose beads and can be recovered by elution with an acetate buffer (pH 5). These findings are consistent with the interpretation that the initiation of DNA synthesis in resting nuclei may be protease dependent and, further, that the cytoplasmic stimulatory factor we have called ADR may be a protease itself.
ACESSO AO ARTIGOhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=304179
- The regulation of DNA synthesis in quiescent lymphocytes by cytoplasmic inhibitors.
- Drug interactions of protease inhibitors.
- Induction of acquired thermotolerance in Tetrahymena thermophila: effects of protein synthesis inhibitors.
- Inhibition of human immunodeficiency virus 1 protease in vitro: rational design of substrate analogue inhibitors.
- Mango flower induction in the brazilian Northeast semi-arid with gibberellin synthesis inhibitors.