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.
Curr Biol
2007 Feb 06;173:213-24. doi: 10.1016/j.cub.2006.12.045.
Show Gene links
Show Anatomy links
A role for Cdc2- and PP2A-mediated regulation of Emi2 in the maintenance of CSF arrest.
Wu Q
,
Guo Y
,
Yamada A
,
Perry JA
,
Wang MZ
,
Araki M
,
Freel CD
,
Tung JJ
,
Tang W
,
Margolis SS
,
Jackson PK
,
Yamano H
,
Asano M
,
Kornbluth S
.
???displayArticle.abstract???
BACKGROUND: Vertebrate oocytes are arrested in metaphase II of meiosis prior to fertilization by cytostatic factor (CSF). CSF enforces a cell-cycle arrest by inhibiting the anaphase-promoting complex (APC), an E3 ubiquitin ligase that targets Cyclin B for degradation. Although Cyclin B synthesis is ongoing during CSF arrest, constant Cyclin B levels are maintained. To achieve this, oocytes allow continuous slow Cyclin B degradation, without eliminating the bulk of Cyclin B, which would induce release from CSF arrest. However, the mechanism that controls this continuous degradation is not understood.
RESULTS: We report here the molecular details of a negative feedback loop wherein Cyclin B promotes its own destruction through Cdc2/Cyclin B-mediated phosphorylation and inhibition of the APC inhibitor Emi2. Emi2 bound to the core APC, and this binding was disrupted by Cdc2/Cyclin B, without affecting Emi2 protein stability. Cdc2-mediated phosphorylation of Emi2 was antagonized by PP2A, which could bind to Emi2 and promote Emi2-APC interactions.
CONCLUSIONS: Constant Cyclin B levels are maintained during a CSF arrest through the regulation of Emi2 activity. A balance between Cdc2 and PP2A controls Emi2 phosphorylation, which in turn controls the ability of Emi2 to bind to and inhibit the APC. This balance allows proper maintenance of Cyclin B levels and Cdc2 kinase activity during CSF arrest.
Bhatt,
The protein kinase p90 rsk as an essential mediator of cytostatic factor activity.
1999, Pubmed,
Xenbase
Bhatt,
The protein kinase p90 rsk as an essential mediator of cytostatic factor activity.
1999,
Pubmed
,
Xenbase
Casaletto,
Inhibition of the anaphase-promoting complex by the Xnf7 ubiquitin ligase.
2005,
Pubmed
,
Xenbase
Fang,
Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1.
1998,
Pubmed
,
Xenbase
Garcia,
Analysis of protein phosphorylation by mass spectrometry.
2005,
Pubmed
Geley,
Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint.
2001,
Pubmed
Gross,
Induction of metaphase arrest in cleaving Xenopus embryos by the protein kinase p90Rsk.
1999,
Pubmed
,
Xenbase
Gross,
The critical role of the MAP kinase pathway in meiosis II in Xenopus oocytes is mediated by p90(Rsk).
2000,
Pubmed
,
Xenbase
Haccard,
Induction of metaphase arrest in cleaving Xenopus embryos by MAP kinase.
1993,
Pubmed
,
Xenbase
Hansen,
CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit.
2006,
Pubmed
,
Xenbase
Hayes,
Early mitotic degradation of Nek2A depends on Cdc20-independent interaction with the APC/C.
2006,
Pubmed
,
Xenbase
Hochegger,
New B-type cyclin synthesis is required between meiosis I and II during Xenopus oocyte maturation.
2001,
Pubmed
,
Xenbase
Kramer,
Activation of the human anaphase-promoting complex by proteins of the CDC20/Fizzy family.
1998,
Pubmed
,
Xenbase
Kubiak,
The metaphase II arrest in mouse oocytes is controlled through microtubule-dependent destruction of cyclin B in the presence of CSF.
1993,
Pubmed
Liu,
Calcium elevation at fertilization coordinates phosphorylation of XErp1/Emi2 by Plx1 and CaMK II to release metaphase arrest by cytostatic factor.
2005,
Pubmed
,
Xenbase
Lorca,
An okadaic acid-sensitive phosphatase negatively controls the cyclin degradation pathway in amphibian eggs.
1991,
Pubmed
,
Xenbase
Margolis,
PP1 control of M phase entry exerted through 14-3-3-regulated Cdc25 dephosphorylation.
2003,
Pubmed
,
Xenbase
Masui,
Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes.
1971,
Pubmed
Murray,
Cell cycle extracts.
1991,
Pubmed
Nutt,
Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2.
2005,
Pubmed
,
Xenbase
Ohsumi,
Emi1-mediated M-phase arrest in Xenopus eggs is distinct from cytostatic factor arrest.
2004,
Pubmed
,
Xenbase
Ohsumi,
Meiosis-specific cell cycle regulation in maturing Xenopus oocytes.
1994,
Pubmed
,
Xenbase
Rauh,
Calcium triggers exit from meiosis II by targeting the APC/C inhibitor XErp1 for degradation.
2005,
Pubmed
,
Xenbase
Reimann,
Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex.
2001,
Pubmed
,
Xenbase
Reimann,
Emi1 is required for cytostatic factor arrest in vertebrate eggs.
2002,
Pubmed
,
Xenbase
Sagata,
The c-mos proto-oncogene product is a cytostatic factor responsible for meiotic arrest in vertebrate eggs.
1989,
Pubmed
,
Xenbase
Schmidt,
Xenopus polo-like kinase Plx1 regulates XErp1, a novel inhibitor of APC/C activity.
2005,
Pubmed
,
Xenbase
Schwab,
Bub1 is activated by the protein kinase p90(Rsk) during Xenopus oocyte maturation.
2001,
Pubmed
,
Xenbase
Sha,
Hysteresis drives cell-cycle transitions in Xenopus laevis egg extracts.
2003,
Pubmed
,
Xenbase
Smythe,
Systems for the study of nuclear assembly, DNA replication, and nuclear breakdown in Xenopus laevis egg extracts.
1991,
Pubmed
,
Xenbase
Tang,
Functional analysis of the spindle-checkpoint proteins using an in vitro ubiquitination assay.
2004,
Pubmed
,
Xenbase
Thibier,
In vivo regulation of cytostatic activity in Xenopus metaphase II-arrested oocytes.
1997,
Pubmed
,
Xenbase
Tsurumi,
The spindle assembly checkpoint is not essential for CSF arrest of mouse oocytes.
2004,
Pubmed
,
Xenbase
Tung,
A role for the anaphase-promoting complex inhibitor Emi2/XErp1, a homolog of early mitotic inhibitor 1, in cytostatic factor arrest of Xenopus eggs.
2005,
Pubmed
,
Xenbase
Tunquist,
The spindle checkpoint kinase bub1 and cyclin e/cdk2 both contribute to the establishment of meiotic metaphase arrest by cytostatic factor.
2002,
Pubmed
,
Xenbase
Tunquist,
Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor-mediated metaphase arrest.
2003,
Pubmed
,
Xenbase
Visintin,
CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis.
1997,
Pubmed
Walsh,
Phosphorylation of the cyclin b1 cytoplasmic retention sequence by mitogen-activated protein kinase and Plx.
2003,
Pubmed
,
Xenbase
Wäsch,
APC-dependent proteolysis of the mitotic cyclin Clb2 is essential for mitotic exit.
2002,
Pubmed
Yamamoto,
APC/C-Cdc20-mediated degradation of cyclin B participates in CSF arrest in unfertilized Xenopus eggs.
2005,
Pubmed
,
Xenbase
Yang,
Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1.
1998,
Pubmed
,
Xenbase
