Vanadate triggers the transition from chromosome condensation to decondensation in a mitotic mutant (tsTM13) inactivation of p34cdc2/H1 kinase and dephosphorylation of mitosis-specific histone H3.
At the nonpermissive temperature (39 degrees C), chromosomes remain condensed in a temperature-sensitive cell mutant (tsTM13) arrested in the late stage of mitosis. Highly increased activity of histone H1 kinase, hyperphosphorylation of histone H1, and mitosis-specific histone H3 phosphorylation are maintained, even in telophase. In the present study, the defect of chromosome decondensation in tsTM13 cells was found to be partially normalized by a tyrosine phosphatase inhibitor, vanadate, with induction of chromosome decondensation and the formation of multinucleated cells. In the presence of vanadate, the H1 kinase activity dropped to near normal levels and the amount of the inactive from of p34cdc2 protein phosphorylated at a tyrosine residue was increased. H1 and H3 were also extensively de- phosphorylated, the latter being tightly associated with chromosome decondensation. Serine/threonine-protein phosphatase in late mitosis of the mutant works normally at 39 degrees C. The results indicate that (a) the genetic defect in the mutant may be involved in the control mechanism of the p34cdc2/H1 kinase activity in the late M phase rather than the phosphatase, (b) normalization of the defect of the mutant by vanadate results from inactivation of H1 kinase, and (c) late mitosis-specific events (p34cdc2/H1 kinase inactivation, mitosis-specific dephosphorylation of histone H1 and H3) are closely operating with chromosome decondensation.
Ajiro
K
K
Aichi Cancer Center, Research Institute, Laboratory of Cell Biology, Chikusa-ku, Japan.
Yasuda
H
H
Tsuji
H
H
D016203:CDC2 Protein Kinase / Q000187:drug effects*; D002875:Chromosomes / Q000187:drug effects* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects* / Q000235:genetics; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000032:analysis; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013696:Temperature; D014638:Vanadates / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D006657:Histones; D014638:Vanadates; D016203:CDC2 Protein Kinase; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases