Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Loss of cell division cycle 2 (Cdc2, also known as Cdk1) activity after cyclin B degradation is necessary, but not sufficient, for mitotic exit. Proteins phosphorylated by Cdc2 and downstream mitotic kinases must be dephosphorylated. We report here that protein phosphatase-1 (PP1) is the main catalyst of mitotic phosphoprotein dephosphorylation. Suppression of PP1 during early mitosis is maintained through dual inhibition by Cdc2 phosphorylation and the binding of inhibitor-1. Protein kinase A (PKA) phosphorylates inhibitor-1, mediating binding to PP1. As Cdc2 levels drop after cyclin B degradation, auto-dephosphorylation of PP1 at its Cdc2 phosphorylation site (Thr 320) allows partial PP1 activation. This promotes PP1-regulated dephosphorylation at the activating site of inhibitor-1 (Thr 35) followed by dissociation of the inhibitor-1-PP1 complex and then full PP1 activation to promote mitotic exit. Thus, Cdc2 both phosphorylates multiple mitotic substrates and inhibits their PP1-mediated dephosphorylation.
Amon,
A decade of Cdc14--a personal perspective. Delivered on 9 July 2007 at the 32nd FEBS Congress in Vienna, Austria.
2008, Pubmed
Amon,
A decade of Cdc14--a personal perspective. Delivered on 9 July 2007 at the 32nd FEBS Congress in Vienna, Austria.
2008,
Pubmed
Axton,
One of the protein phosphatase 1 isoenzymes in Drosophila is essential for mitosis.
1990,
Pubmed
Azzam,
Phosphorylation by cyclin B-Cdk underlies release of mitotic exit activator Cdc14 from the nucleolus.
2004,
Pubmed
Bailis,
Pachytene exit controlled by reversal of Mek1-dependent phosphorylation.
2000,
Pubmed
Bianchi,
Binding of phosphatase-1 delta to the retinoblastoma protein pRb involves domains that include substrate recognition residues and a pRB binding motif.
2001,
Pubmed
Bibb,
Phosphorylation of protein phosphatase inhibitor-1 by Cdk5.
2001,
Pubmed
Casaletto,
Inhibition of the anaphase-promoting complex by the Xnf7 ubiquitin ligase.
2005,
Pubmed
,
Xenbase
Ceulemans,
Functional diversity of protein phosphatase-1, a cellular economizer and reset button.
2004,
Pubmed
Che,
A phosphatase activity in Xenopus oocyte extracts preferentially dephosphorylates the MPM-2 epitope.
1998,
Pubmed
,
Xenbase
Chen,
Multiple protein phosphatases are required for mitosis in Drosophila.
2007,
Pubmed
Dohadwala,
Phosphorylation and inactivation of protein phosphatase 1 by cyclin-dependent kinases.
1994,
Pubmed
Doonan,
The bimG gene of Aspergillus nidulans, required for completion of anaphase, encodes a homolog of mammalian phosphoprotein phosphatase 1.
1989,
Pubmed
El-Armouche,
Role of calcineurin and protein phosphatase-2A in the regulation of phosphatase inhibitor-1 in cardiac myocytes.
2006,
Pubmed
Higuchi,
Phosphorylation of protein phosphatase-1 inhibitors, inhibitor-1 and DARPP-32, in renal medulla.
2000,
Pubmed
Kotani,
PKA and MPF-activated polo-like kinase regulate anaphase-promoting complex activity and mitosis progression.
1998,
Pubmed
Kwon,
Cell cycle-dependent phosphorylation of mammalian protein phosphatase 1 by cdc2 kinase.
1997,
Pubmed
Lew,
Regulatory roles of cyclin dependent kinase phosphorylation in cell cycle control.
1996,
Pubmed
Margolis,
PP1 control of M phase entry exerted through 14-3-3-regulated Cdc25 dephosphorylation.
2003,
Pubmed
,
Xenbase
Margolis,
A role for PP1 in the Cdc2/Cyclin B-mediated positive feedback activation of Cdc25.
2006,
Pubmed
,
Xenbase
Mochida,
Calcineurin is required to release Xenopus egg extracts from meiotic M phase.
2007,
Pubmed
,
Xenbase
Murray,
Cell cycle extracts.
1991,
Pubmed
Nishiyama,
Transient activation of calcineurin is essential to initiate embryonic development in Xenopus laevis.
2007,
Pubmed
,
Xenbase
Queralt,
Cdk-counteracting phosphatases unlock mitotic exit.
2008,
Pubmed
Skoufias,
Mitosis persists in the absence of Cdk1 activity when proteolysis or protein phosphatase activity is suppressed.
2007,
Pubmed
Snyder,
Phosphorylation of DARPP-32 and protein phosphatase inhibitor-1 in rat choroid plexus: regulation by factors other than dopamine.
1992,
Pubmed
Stegmeier,
Closing mitosis: the functions of the Cdc14 phosphatase and its regulation.
2004,
Pubmed
Trautmann,
Cell cycle: new functions for Cdc14 family phosphatases.
2002,
Pubmed
Wolfe,
Phospho-regulation of the Cdc14/Clp1 phosphatase delays late mitotic events in S. pombe.
2006,
Pubmed
Wu,
A role for Cdc2- and PP2A-mediated regulation of Emi2 in the maintenance of CSF arrest.
2007,
Pubmed
,
Xenbase
