Rca1 inhibits APC-Cdh1(Fzr) and is required to prevent cyclin degradation in G2.
We demonstrate that Rca1 is an essential inhibitor of the anaphase-promoting complex/cyclosome (APC) in Drosophila. APC activity is restricted to mitotic stages and G1 by its activators Cdc20-Fizzy (Cdc20(Fzy)) and Cdh1-Fizzy-related (Cdh1(Fzr)), respectively. In rca1 mutants, cyclins are degraded prematurely in G2 by APC-Cdh1(Fzr)-dependent proteolysis, and cells fail to execute mitosis. Overexpression of Cdh1(Fzr) mimics the rca1 phenotype, and coexpression of Rca1 blocks this Cdh1(Fzr) function. We show that Rca1 and Cdh1(Fzr) are in a complex that also includes the APC component Cdc27. Previous studies have shown that phosphorylation of Cdh1 prevents its interaction with the APC. Our data reveal a different mode of APC regulation by Rca1 at the G2 stage, when low Cdk activity is unable to inhibit Cdh1(Fzr) interaction.
Grosskortenhaus
Ruth
R
Department of Genetics, Weyertal 121, University of Cologne, 50931 Cologne, Germany.
Sprenger
Frank
F
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism*; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D019927:Cyclin E / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins; D004843:Epistasis, Genetic; D016195:G2 Phase / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D008025:Ligases / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D016296:Mutagenesis / Q000502:physiology; D010641:Phenotype; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; C577365:Cdc27 protein, Drosophila; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D019927:Cyclin E; D029721:Drosophila Proteins; D008565:Membrane Proteins; C491136:Rca1 protein, Drosophila; C577674:fzr protein, Drosophila; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases; D008025:Ligases