Abstract
Stage-specific proteolysis of mitotic cyclins is fundamental to eukaryotic cell cycle regulation. We found that yeast Hct1, a conserved protein of eukaryotes, is a necessary and rate-limiting component of this proteolysis pathway. In hct1 mutants, the mitotic cyclin Clb2 is highly stabilized and inappropriately induces DNA replication, while G1 cyclins and other proteolytic substrates remain short-lived. Viability of hct1 mutants depends on SIC1. This and further results suggest that inhibition of cyclin-dependent kinases may compensate for defects in cyclin proteolysis. Remarkably, elevated levels of Hct1 ectopically activate destruction box- and Cdc23-dependent degradation of Clb2 and cause phenotypic effects characteristic for a depletion of M-phase cyclins. Hct1 and the related Cdc20 may function as substrate-specific regulators of proteolysis during mitosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Anaphase-Promoting Complex-Cyclosome
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Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome
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Cdc20 Proteins
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Cdh1 Proteins
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cyclin B*
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Cyclin-Dependent Kinases / antagonists & inhibitors
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Cyclins / metabolism*
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Down-Regulation
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Fungal Proteins / genetics
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Fungal Proteins / metabolism*
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Fungal Proteins / physiology*
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Gene Dosage
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Mitosis
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Molecular Sequence Data
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Saccharomyces cerevisiae
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Saccharomyces cerevisiae Proteins*
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Ubiquitin-Protein Ligase Complexes
Substances
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Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome
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CDC20 protein, S cerevisiae
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CDC23 protein, S cerevisiae
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CDH1 protein, S cerevisiae
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CLB2 protein, S cerevisiae
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Cdc20 Proteins
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Cdh1 Proteins
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Cell Cycle Proteins
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Cyclin B
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Cyclins
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Fungal Proteins
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Saccharomyces cerevisiae Proteins
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Ubiquitin-Protein Ligase Complexes
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Anaphase-Promoting Complex-Cyclosome
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Cyclin-Dependent Kinases
Associated data
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GENBANK/U05340
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GENBANK/Z72525