Cell cycle-dependent nuclear export of Cdh1p may contribute to the inactivation of APC/C(Cdh1).
Cdh1p is a substrate-specific subunit of the anaphase-promoting complex (APC/C), which functions as an E3 ubiquitin ligase to degrade the mitotic cyclin Clb2p and other substrates during the G(1) phase of the cell cycle. Cdh1p is phosphorylated and thereby inactivated at the G(1)/S transition predominantly by Cdc28p-Clb5p. Here we show that Cdh1p is nuclear during the G(1) phase of the cell cycle, but redistributes to the cytoplasm between S phase and the end of mitosis. Nuclear export of Cdh1p is regulated by phosphorylation and requires active Cdc28p kinase. Cdh1p binds to the importin Pse1p and the exportin Msn5p, which is necessary and sufficient to promote efficient export of Cdh1p in vivo. Although msn5delta cells are viable, they are sensitive to Cdh1p overexpression. Likewise, a mutant form of Cdh1p, which is constitutively nuclear, prevents accumulation of Clb2p and leads to cell cycle arrest when overexpressed in wild-type cells. Taken together, these results suggest that phosphorylation-dependent nuclear export of Cdh1p by Msn5p contributes to efficient inactivation of APC/C(Cdh1).
Jaquenoud
Malika
M
Swiss Institute for Experimental Cancer Research (ISREC), Chemin des Boveresses 155, 1066 Epalinges/VD, Switzerland.
van Drogen
Frank
F
Peter
Matthias
M
D021581:Active Transport, Cell Nucleus; D064173:Anaphase-Promoting Complex-Cyclosome; D002352:Carrier Proteins / Q000378:metabolism; D064199:Cdc20 Proteins; D064200:Cdh1 Proteins; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D028884:Karyopherins; D008025:Ligases / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes
C577495:CDC20 protein, S cerevisiae; C577583:CDH1 protein, S cerevisiae; D002352:Carrier Proteins; D064199:Cdc20 Proteins; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D028884:Karyopherins; C401306:MSN5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D008025:Ligases