Effects of proteasome inhibitor (lactacystin) and cysteine protease inhibitor (E-64-d) on processes of mitosis in Xenopus embryonic cells.
At least two different protease pathways have been implicated in the degradation that is required to control the eukaryotic cell cycle; these two pathways center on the activities of ubiquitin/proteasome and cysteine protease. The proteasome inhibitors, lactacystin and AcLLnL and the cysteine protease inhibitor E-64-d were tested for their ability to inhibit the cell cycles of Xenopus embryos. Lactacystin, AcLLnL and E-64-d all caused the complete arrest of the cell cycle. To define the specific cell cycle processes that were affected by the two inhibitors, we performed a cytological analysis. Inhibition of the cell cycle by lactacystin and E-64-d occurred during prophase and metaphase. The number of cells that arrested in prophase was 1.4-times higher in the E-64-d-treated group than in the control group and the number of arrested cells in the lactacystin-treated group was 1.4-times higher than in the E-64-d-treated group. The number of cells that arrested in metaphase was 3-to-4-times higher in the E-64-d and lactacystin groups than in the control group. These results indicate that both cysteine protease(s) and proteasomes are involved in the prophase and metaphase stages of cell division.
Sekiguchi
Tomohiro
T
Laboratory of Biochemistry, College of Humanities and Sciences, Nihon University, Tokyo, Japan.
Hosoyama
Yoshiyuki
Y
Miyata
Shohei
S
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000187:drug effects*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects*; D015398:Signal Transduction; D014981:Xenopus / Q000196:embryology*
D015853:Cysteine Proteinase Inhibitors; C067713:lactacystin; D007930:Leucine; C108192:aloxistatin; D000111:Acetylcysteine