Hansen DV et al. (2006), CaMKII and polo-like kinase 1 sequentially phos...

XB-ART-860

Proc Natl Acad Sci U S A 2006 Jan 17;1033:608-13. doi: 10.1073/pnas.0509549102.

Show Gene links Show Anatomy links

CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit.

Hansen DV , Tung JJ , Jackson PK .

???displayArticle.abstract???
In vertebrate meiosis, unfertilized eggs are arrested in metaphase II by cytostatic factor (CSF), which is required to maintain mitotic cyclin-dependent kinase activity. Fertilization triggers a transient increase in cytosolic free Ca(2+), which leads to CSF inactivation and ubiquitin-dependent cyclin destruction through the anaphase promoting complex or cyclosome (APC/C). The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and the Polo-like kinase Plx1 are essential factors for Ca(2+)-induced meiotic exit, but the critical targets of these kinases were unknown. The APC/C inhibitor Emi2 or XErp1 has recently been characterized as a pivotal CSF component, required to maintain metaphase II arrest and rapidly destroyed in response to Ca(2+) signaling through phosphorylation by Plx1 and ubiquitination by the SCF(betaTrCP) complex. An important question is how the increase in free Ca(2+) targets Plx1 activity toward Emi2. Here, we demonstrate that CaMKII is required for Ca(2+)-induced Emi2 destruction, and that CaMKII functions as a "priming kinase," directly phosphorylating Emi2 at a specific motif to induce a strong interaction with the Polo Box domain of Plx1. We show that the strict requirement for CaMKII to phosphorylate Emi2 is a specific feature of CSF arrest, and we also use phosphatase inhibitors to demonstrate an additional mode of Emi2 inactivation independent of its destruction. We firmly establish the CSF component Emi2 as the first-known critical and direct target of CaMKII in CSF release, providing a detailed molecular mechanism explaining how CaMKII and Plx1 coordinately direct APC/C activation and meiotic exit upon fertilization.

???displayArticle.pubmedLink??? 16407128
???displayArticle.pmcLink??? PMC1325965
???displayArticle.link??? Proc Natl Acad Sci U S A
???displayArticle.grants??? [+]

Species referenced: Xenopus
Genes referenced: camk2g fbxo43 plk1

References [+] :

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
Brassac, The polo-like kinase Plx1 prevents premature inactivation of the APC(Fizzy)-dependent pathway in the early Xenopus cell cycle. 2000, Pubmed , Xenbase
Colbran, Regulatory domain of calcium/calmodulin-dependent protein kinase II. Mechanism of inhibition and regulation by phosphorylation. 1989, Pubmed
Descombes, The polo-like kinase Plx1 is required for M phase exit and destruction of mitotic regulators in Xenopus egg extracts. 1998, Pubmed , Xenbase
Dumont, p90Rsk is not involved in cytostatic factor arrest in mouse oocytes. 2005, Pubmed , Xenbase
Elia, Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates. 2003, Pubmed
Furuno, Suppression of DNA replication via Mos function during meiotic divisions in Xenopus oocytes. 1994, Pubmed , Xenbase
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
Hansen, Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1. 2004, Pubmed , Xenbase
Liu, The polo box is required for multiple functions of Plx1 in mitosis. 2004, Pubmed , Xenbase
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
Lorca, Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF upon fertilization of Xenopus eggs. 1993, Pubmed , Xenbase
Madgwick, Calmodulin-dependent protein kinase II, and not protein kinase C, is sufficient for triggering cell-cycle resumption in mammalian eggs. 2005, Pubmed
Margottin-Goguet, Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. 2003, Pubmed , Xenbase
Masui, Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes. 1971, Pubmed
Matsumoto, Calcium, calmodulin, and CaMKII requirement for initiation of centrosome duplication in Xenopus egg extracts. 2002, Pubmed , Xenbase
Murray, The role of cyclin synthesis and degradation in the control of maturation promoting factor activity. 1989, Pubmed , Xenbase
Ohsumi, Emi1-mediated M-phase arrest in Xenopus eggs is distinct from cytostatic factor arrest. 2004, Pubmed , Xenbase
Paronetto, Functional interaction between p90Rsk2 and Emi1 contributes to the metaphase arrest of mouse oocytes. 2004, Pubmed
Rauh, Calcium triggers exit from meiosis II by targeting the APC/C inhibitor XErp1 for degradation. 2005, Pubmed , Xenbase
Reimann, Emi1 is required for cytostatic factor arrest in vertebrate eggs. 2002, Pubmed , Xenbase
Reimann, Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. 2001, Pubmed , Xenbase
Runft, Egg activation at fertilization: where it all begins. 2002, Pubmed
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
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, Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggs. 2003, Pubmed , Xenbase
Tunquist, Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor-mediated metaphase arrest. 2003, Pubmed , Xenbase