Abstract
Sister chromatid separation during exit from mitosis requires separase. Securin inhibits separase during the cell cycle until metaphase when it is degraded by the anaphase-promoting complex/cyclosome (APC/C). In Drosophila, sister chromatid separation proceeds even in the presence of stabilized securin with mutations in its D-box, a motif known to mediate recruitment to the APC/C. Alternative pathways might therefore regulate separase and sister chromatid separation apart from proteolysis of the Drosophila securin PIM. Consistent with this proposal and with results from yeast and vertebrates, we show here that the effects of stabilized securin with mutations in the D-box are enhanced in vivo by reduced Polo kinase function or by mitotically stabilized Cyclin A. However, we also show that PIM contains a KEN-box, which is required for mitotic degradation in addition to the D-box, and that sister chromatid separation is completely inhibited by PIM with mutations in both degradation signals.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs / genetics
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Amino Acid Sequence
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Anaphase / genetics*
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Anaphase-Promoting Complex-Cyclosome
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Animals
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Cell Cycle Proteins / genetics*
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Cell Cycle Proteins / metabolism
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Cyclin A / genetics*
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Cyclin A / metabolism
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Drosophila Proteins / genetics*
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Drosophila Proteins / metabolism
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Drosophila melanogaster / cytology
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Drosophila melanogaster / genetics*
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Drosophila melanogaster / metabolism*
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Endopeptidases / genetics
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Endopeptidases / metabolism
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Gene Expression Regulation / genetics
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Mitosis / genetics
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Molecular Sequence Data
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Mutation / genetics
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Protein Serine-Threonine Kinases / genetics
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Separase
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Signal Transduction / genetics
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Ubiquitin-Protein Ligase Complexes / genetics
Substances
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Cell Cycle Proteins
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Cyclin A
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Drosophila Proteins
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PIM protein, Drosophila
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Ubiquitin-Protein Ligase Complexes
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Anaphase-Promoting Complex-Cyclosome
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polo protein, Drosophila
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Protein Serine-Threonine Kinases
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Endopeptidases
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Separase
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Sse protein, Drosophila