Ubiquitin dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant ts85

Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85

https://www.cell.com/cell/pdf/0092-8674(88)90060-8.pdf

cdc2 is a component of the M phase-specific histone H1 kinase: Evidence for identity with MPF

Mitotic induction and maintenance by overexpression of a G2-specific gene that encodes a potential protein kinase

https://www.cell.com/cell/pdf/0092-8674(80)90367-0.pdf

Nerve growth factor mediates phosphorylation of specific proteins.

Changes in the structural organisation of chromatin are necessary for the progression of the cell cycle. These changes are thought to be regulated mainly by the modification of chromosomal proteins by reactions such as phosphorylation1–8, acetylation9–12, methylation13,14 and poly(ADP-ribosyl)-ation15,16. Among these modifications, phosphorylation of histones, especially that of the H1 histone, is the most likely candidate for a factor which regulates chromosome condensation1–8. It has been proposed that the phosphorylated form of H1 histone may be involved in the initiation of chromosome condensation1–4 or in the maintenance of the condensed state of chromatin8. The latter possibility is unlikely because zinc chloride, which inhibits phosphatase in vivo and preserves the highly phosphorylated form of H1 histone at metaphase, does not prevent the dispersion of chromosomes at the end of mitosis17. As for the former possibility, Bradbury et al. reported2 that the activity of H1 histone phosphorylation is closely correlated with mitotic triggering in the cell cycle and suggest3,4 that H1 histone phosphokinase is involved in the initiation of mitosis. However, no causal relationship has been established. To analyse the mechanism of the progression of the cell cycle, we have isolated several temperature-sensitive (ts) growth mutants from FM3A, a cell line derived from C3H mouse mammary carcinoma18. We report here on one of these ts mutants, designated the ts85 strain, which shows an abnormal chromosome condensation as well as deficiency in H1 histone phosphorylation at the non-permissive temperature. Our results support the hypothesis that H1 histone phosphorylation controls the initiation step of mitosis through chromosome condensation.

Tohru Marunouchi

Papers

Evidence for the involvement of H1 histone phosphorylation in chromosome condensation