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Cell cycle‐dependent nuclear export of Cdh1p may contribute to the inactivation of APC/C Cdh1
Author(s) -
Jaquenoud Malika,
van Drogen Frank,
Peter Matthias
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf634
Subject(s) - library science , art history , operations research , art , engineering , computer science
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 msn5 Δ cells are viable, they are sensitive to Cdh1p overexpression. Likewise, a mutant form of Cdh1p, which is consitutively 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 .