Inhibition of histone phosphorylation by staurosporine leads to chromosome decondensation.
In mammalian cells, hyperphosphorylation of histone H1 and phosphorylation of histone H3 correlate well with the G2 phase to metaphase condensation of chromosomes, and these phosphorylations most probably have a role in initiating and controlling the entry into mitosis. The protein kinase inhibitor staurosporine has been used to examine the role of H1 and H3 phosphorylations in controlling chromosome condensation in the mouse FM3A cell line. We present evidence that (i) staurosporine inhibits the protein kinases that phosphorylate histone H1 during mitosis, (ii) staurosporine also inhibits the histone H3-specific kinase, (iii) the inhibition of these kinase activities prevent cells from entering mitosis, and (iv) addition of staurosporine to cells already arrested at metaphase by nocodazole causes a rapid dephosphorylation of histones H1 and H3 and the decondensation of the metaphase chromosomes. The results show that the hyperphosphorylation of histone H1 and phosphorylation of histone H3 are required to maintain metaphase chromosomes in their condensed state.
Th'ng
J P
JP
Department of Biological Chemistry School of Medicine, University of California, Davis 95616.
Guo
X W
XW
Swank
R A
RA
Crissman
H A
HA
Bradbury
E M
EM
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002875:Chromosomes / Q000187:drug effects* / Q000648:ultrastructure; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D006657:Histones / Q000302:isolation & purification / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental; D008677:Metaphase / Q000187:drug effects; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D006656:Protamine Kinase / Q000037:antagonists & inhibitors*; D019311:Staurosporine; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D006657:Histones; D010750:Phosphoproteins; D006656:Protamine Kinase; D019311:Staurosporine