The Spo12 protein of Saccharomyces cerevisiae: a regulator of mitotic exit whose cell cycle-dependent degradation is mediated by the anaphase-promoting complex
| Autor: | Rajvee Shah, Anthony L. Johnson, Leland H. Johnston, Sanne Jensen, Lisa M. Frenz |
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| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Time Factors
Cyclin B Cell Cycle Proteins Cdh1 Proteins Nuclear protein Fluorescent Antibody Technique Indirect Cyclin-Dependent Kinase Inhibitor Proteins Genetics biology Cell Cycle Temperature Nuclear Proteins Cell cycle Cyclin-Dependent Kinases Cell biology Meiosis Phenotype CDC28 Protein Kinase S cerevisiae Cell Nucleolus Research Article Plasmids Saccharomyces cerevisiae Proteins Genotype Molecular Sequence Data Mitosis Saccharomyces cerevisiae Protein Serine-Threonine Kinases Models Biological Fungal Proteins Amino Acid Sequence Cell Nucleus Sequence Homology Amino Acid Cdc14 G1 Phase Galactose Diploidy Glucose Microscopy Fluorescence Mitotic exit Mutation biology.protein Mutagenesis Site-Directed Anaphase-promoting complex Protein Tyrosine Phosphatases Anaphase Protein Kinases Cyclin-dependent kinase inhibitor protein |
| Popis: | The Spo12 protein plays a regulatory role in two of the most fundamental processes of biology, mitosis and meiosis, and yet its biochemical function remains elusive. In this study we concentrate on the genetic and biochemical analysis of its mitotic function. Since high-copy SPO12 is able to suppress a wide variety of mitotic exit mutants, all of which arrest with high Clb-Cdc28 activity, we speculated whether SPO12 is able to facilitate exit from mitosis when overexpressed by antagonizing mitotic kinase activity. We show, however, that Spo12 is not a potent regulator of Clb-Cdc28 activity and can function independently of either the cyclin-dependent kinase inhibitor (CDKi), Sic1, or the anaphase-promoting complex (APC) regulator, Hct1. Spo12 protein level is regulated by the APC and the protein is degraded in G1 by an Hct1-dependent mechanism. We also demonstrate that in addition to localizing to the nucleus Spo12 is a nucleolar protein. We propose a model where overexpression of Spo12 may lead to the delocalization of a small amount of Cdc14 from the nucleolus, resulting in a sufficient lowering of mitotic kinase levels to facilitate mitotic exit. Finally, site-directed mutagenesis of highly conserved residues in the Spo12 protein sequence abolishes both its mitotic suppressor activity as well as its meiotic function. This result is the first indication that Spo12 may carry out the same biochemical function in mitosis as it does in meiosis. |
| Databáze: | OpenAIRE |
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