Chromosome condensation induced by fostriecin does not require p34cdc2 kinase activity and histone H1 hyperphosphorylation, but is associated with enhanced histone H2A and H3 phosphorylation.
Chromosome condensation at mitosis correlates with the activation of p34cdc2 kinase, the hyperphosphorylation of histone H1 and the phosphorylation of histone H3. Chromosome condensation can also be induced by treating interphase cells with the protein phosphatase 1 and 2A inhibitors okadaic acid and fostriecin. Mouse mammary tumour FT210 cells grow normally at 32 degrees C, but at 39 degrees C they lose p34cdc2 kinase activity and arrest in G2 because of a temperature-sensitive lesion in the cdc2 gene. The treatment of these G2-arrested FT210 cells with fostriecin or okadaic acid resulted in full chromosome condensation in the absence of p34cdc2 kinase activity or histone H1 hyperphosphorylation. However, phosphorylation of histones H2A and H3 was strongly stimulated, partly through inhibition of histone H2A and H3 phosphatases, and cyclins A and B were degraded. The cells were unable to complete mitosis and divide. In the presence of the protein kinase inhibitor starosporine, the addition of fostriecin did not induce histone phosphorylation and chromosome condensation. The results show that chromosome condensation can take place without either the histone H1 hyperphosphorylation or the p34cdc2 kinase activity normally associated with mitosis, although it requires a staurosporine-sensitive protein kinase activity. The results further suggest that protein phosphatases 1 and 2A may be important in regulating chromosome condensation by restricting the level of histone phosphorylation during interphase, thereby preventing premature chromosome condensation.
Guo
X W
XW
Department of Biological Chemistry, University of California, Davis 95616.
Th'ng
J P
JP
Swank
R A
RA
Anderson
H J
HJ
Tudan
C
C
Bradbury
E M
EM
Roberge
M
M
D000470:Alkaloids / Q000494:pharmacology; D000475:Alkenes / Q000494:pharmacology; D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D002875:Chromosomes / Q000502:physiology*; D016213:Cyclins / Q000378:metabolism; D004988:Ethers, Cyclic / Q000494:pharmacology; D016195:G2 Phase; D018816:Genes, cdc / Q000235:genetics; D006657:Histones / Q000378:metabolism*; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011090:Polyenes; D006656:Protamine Kinase / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D054645:Protein Phosphatase 1; D011753:Pyrones; D019311:Staurosporine; D013696:Temperature; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000475:Alkenes; D016213:Cyclins; D004988:Ethers, Cyclic; D006657:Histones; D011090:Polyenes; D011753:Pyrones; D019319:Okadaic Acid; D006656:Protamine Kinase; D011493:Protein Kinase C; D016203:CDC2 Protein Kinase; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D019311:Staurosporine; C040313:fostriecin