Abstract
Regulation of G2 phase is based on inhibition of MPF (M-phase Promoting Factor) through phosphorylation by Wee1-like kinases. Removal of the inhibiting phosphate group requires Cdc25-like phosphatases. In fission yeast, size control is achieved by monitoring cell length via interactions of Pom1, Nif1, Cdr1 and Cdr2 proteins, regulating MPF via the Wee1 kinase. Here, a search for homologues of these key proteins was performed in the genomes of several model organisms to analyze the evolution of G2 size control. Both the known upstream pathways regulating Wee1 protein (Pom1 → Cdr2, and Nif1 → Cdr1) have been found to be characteristic only in fission yeasts. Mik1, a backup copy of Wee1 kinase probably appeared in the common ancestor of the fission yeasts. The duplication resulting in Wee1A and Wee1B isoforms probably happened in a common ancestor of higher animals, while the Myt1 protein (found only in animals) could be a variant between an ancient serine / threonine kinase and the Wee1 tyrosine kinase. Probably both the ancestors of plants and that of fungi may have lost the myt1 gene. In fission yeasts, Pyp3 is a backup phosphatase of Cdc25, also activating MPF in late G2. Interestingly, we found that the small Ibp1 phosphatase appeared to be a closer homologue of Cdc25, although its function is different. Moreover, Cdc25 homologues identified in plants were found to be more closely related to Ibp1 rather than to Cdc25 of fission yeast. In the Cdc25-like proteins, a novel conserved region was found with the consensus sequence LxxG(Y/F).
Highlights
G2 phase size control is based on the inhibition of a cyclin / cyclin-dependent kinase (Cdk) heterodimer called MPF (M-phase promoting factor), until a critical cell size is reached
3 Results 3.1 Homologous proteins found in different databases Pom1 is the only known DYRK kinase (Dual-specificity Tyrosine Regulated Kinase) in fission yeast, so BLAST and reciprocal BLAST searches have found sequence homology to several DYRK kinases in the tested organisms, their protein length is significantly different from that of Pom1
Wee1 and Cdc25 proteins generally have homologs in the wildlife, we examined them among the proteins of model organisms with fully sequenced genomes
Summary
G2 phase size control is based on the inhibition of a cyclin / cyclin-dependent kinase (Cdk) heterodimer called MPF (M-phase promoting factor), until a critical cell size is reached. In the G2 phase of the cell cycle, the Tyr-15 amino acid of the regulatory Cdk subunit of MPF is phosphorylated by the Wee kinase, generating the low-activity form of MPF, called pre-MPF. In late G2 phase, the inhibiting phosphate group is removed by the Cdc phosphatase, producing the high-activity MPF form (Fig. 1). MPF once directly phosphorylates several substrates to initiate mitosis, regulates itself by activating the Cdc phosphatase (positive feedback loop), and by inhibition of the Wee kinase (double negative feedback) to ensure a rapid entry into M phase (Fig. 1) [1]. In the fission yeast Schizosaccharomyces pombe (fission yeast), size control in G2 phase is of paramount importance, backup copies of both Cdc phosphatase and Wee kinase exist, namely Pyp phosphatase and Mik kinase, respectively. Size control may probably be achieved via monitoring cell length through Pom, Nif, Cdr (Nim1) and Cdr proteins (Fig. 1), all being upstream regulators of Wee1 [2]
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