Torres MP and Borchers CH (2007) Mitotic Phosphorylation of the Anaphase-promoting Complex Inhibitory Subunit Mnd2 Is Necessary for Efficient Progression through Meiosis I. J Biol Chem 282(24):17351-62
Abstract: The yeast APC subunit, Mnd2, is necessary for maintaining sister chromatid cohesion in prophase I of meiosis by inhibiting premature ubiquitination and subsequent degradation of substrates by the APC(Ama1) ubiquitin ligase. In a proteomics screen for post-translational modifications on the APC, we discovered that Mnd2 is phosphorylated during mitosis in a cell cycle dependent manner. We have identified and characterized the sites of mitotic Mnd2 phosphorylation during the cell cycle. Collective mutation of Mnd2 phosphorylation sites to alanine had no effect on vegetative growth, but a striking effect (>85% reduction) on the percentage of tetrad forming cells compared to the wild type strain. Similar to the MND2 deletion strain, cells harboring the alanine mutant that did not form spores arrested after pre-meiotic S-phase with a single undivided nucleus and low levels of the APC(Ama1) meiotic substrate, Clb5, relative to wild type cells. In contrast, collective mutation of Mnd2 phosphorylation sites to aspartic acid resulted in partial suppression of the sporulation defect. No differences were observed in the binding between each Mnd2 isoform and the APC in vitro. However, in vivo, we observed a gradient in the abundance of APC-associated Mnd2 in each strain, which was proportional to the observed differences in sporulation and Clb5 levels. Taken together, these data suggest that mitotic phosphorylation of Mnd2 is necessary for APC-mediated progression beyond the first meiotic nuclear division.
|Status: Published||Type: Journal Article||PubMed ID: 17459880|
Topics addressed in this paper
Number of different genes curated to this paper: 3
- To go to the Locus page for a gene, click on the gene name.