APC/CCdh1-mediated degradation of Cdh1 during meiosis in S. cerevisiae

Abstract

The Anaphase-Promoting Complex/Cyclosome (APC/C) is a ubiquitin ligase that promotes the ubiquitination and subsequent degradation of numerous cell cycle regulators during mitosis and in G1. Proteins are recruited to the APC/C by activator proteins such as Cdh1. During the cell cycle, Cdh1 is subject to precise regulation so that substrates are not degraded prematurely. We have explored the regulation of Cdh1 during the developmental transition into meiosis and sporulation in the budding yeast S. cerevisiae. Transition to sporulation medium triggers the degradation of Cdh1. Degradation requires that cells be of the a/a mating type and be starved for glucose, but they do not actually need to enter into the meiotic program. Degradation requires an intact SNF1 protein kinase complex (orthologous to the mammalian AMPK nutritional sensor), which is activated by the absence of glucose. Cdh1 degradation is mediated by the APC/C itself in a trans mechanism in which one molecule of Cdh1 recruits a second molecule of Cdh1 to the APC/C for ubiquitination. However, Cdh1-Cdh1 recognition does not depend on the degradation motifs or binding sites involved in the recognition of typical APC/C substrates. We hypothesize that Cdh1 degradation is necessary for the preservation of cell cycle regulators and chromosome cohesion proteins between the reductional and equational meiotic divisions, which occur without the intervening Gap or S phases found in mitotic cell cycles.