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

Abstract

A so-called "growth-associated" or "M phase-specific" histone H1 kinase (H1K) has been described in a wide variety of eukaryotic cell types. In starfish oocytes, the hormone 1-methyladenine triggers synchronous meiotic divisions that are accompanied by a rapid 30-fold stimulation of H1K activity. We have substantially purified this activated enzyme and find that it is enriched for a protein of 34 kd. Quantitative immunoblotting of the column fractions with antibodies raised against p34, the product of the fission yeast cdc2 gene, revealed complete coelution of the H1K activity and a 34 kd anti-cdc2 cross-reactive protein. Starfish H1K also displayed the same apparent molecular weight, on a molecular sizing column, as the mitotically activated p13/p34/p62 protein kinase complex of HeLa cells. p13, the product of the fission yeast suc1+ gene, interacts tightly with p34 in yeast, Xenopus, and HeLa cells. H1K from starfish binds strongly to p13-Sepharose and the time course of 1-methyladenine-induced H1K activation, whether assayed in crude extract or on p13-Sepharose beads, is identical. These results indicate that a cdc2 homolog is a subunit of the M phase-specific H1K of starfish meiotic oocytes. Since this protein is also a subunit of the M-phase promoting factor (MPF) of Xenopus oocytes, we suggest that H1K and MPF are the same entity, and that histone H1 is likely to be one substrate of the pleiotropic MPF.