Requirement of Cks2 for the First Metaphase/Anaphase Transition of Mammalian Meiosis

Spruck, Charles; Miguel, María P. De; Smith, Adrian; Ryan, Aimee K.; Stein, Paula; Schultz, Richard M.; Lincoln, A. Jeannine; Donovan, Peter; Reed, Steven I.

doi:10.1126/science.1084149

Cited by 109 publications

(122 citation statements)

References 17 publications

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“…Alternatively, regulation of Cdc2 by Cks proteins may also dictate differential kinase activity. It was reported that knockout of Cks2 in mouse promoted an MI arrest, though the reason for this was unclear (Spruck et al, 2003). It is possible that loss of Cks2 in the knockout lowered Cdc2 kinase activity in meiosis I, leading to inappropriate Emi2 stabilization.…”

Section: Cdc2 Kinase Activity In the Control Of Emi2 Stabilitymentioning

confidence: 99%

Cdc2 and Mos Regulate Emi2 Stability to Promote the Meiosis I–Meiosis II Transition

Tang

Guo

et al. 2008

MBoC

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The transition of oocytes from meiosis I (MI) to meiosis II (MII) requires partial cyclin B degradation to allow MI exit without S phase entry. Rapid reaccumulation of cyclin B allows direct progression into MII, producing a cytostatic factor (CSF)-arrested egg. It has been reported that dampened translation of the anaphase-promoting complex (APC) inhibitor Emi2 at MI allows partial APC activation and MI exit. We have detected active Emi2 translation at MI and show that Emi2 levels in MI are mainly controlled by regulated degradation. Emi2 degradation in MI depends not on Ca2+/calmodulin-dependent protein kinase II (CaMKII), but on Cdc2-mediated phosphorylation of multiple sites within Emi2. As in MII, this phosphorylation is antagonized by Mos-mediated recruitment of PP2A to Emi2. Higher Cdc2 kinase activity in MI than MII allows sufficient Emi2 phosphorylation to destabilize Emi2 in MI. At MI anaphase, APC-mediated degradation of cyclin B decreases Cdc2 activity, enabling Cdc2-mediated Emi2 phosphorylation to be successfully antagonized by Mos-mediated PP2A recruitment. These data suggest a model of APC autoinhibition mediated by stabilization of Emi2; Emi2 proteins accumulate at MI exit and inhibit APC activity sufficiently to prevent complete degradation of cyclin B, allowing MI exit while preventing interphase before MII entry.

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Section: Cdc2 Kinase Activity In the Control Of Emi2 Stabilitymentioning

confidence: 99%

Cdc2 and Mos Regulate Emi2 Stability to Promote the Meiosis I–Meiosis II Transition

Tang

Guo

et al. 2008

MBoC

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“…CKS2 is involved in the process of germ cell progression past the first meiotic cell division (Spruck et al, 2003); PSME2 is a proteasome activator involved in enhancing class I major hisocompatibility complex antigen presentation (Preckel et al, 1999); and DHFR is involved in the conversion of dihydrofolic acid into tetrahydrofolic acid, a carrier for the methyl group required for de novo synthesis of a variety of essential metabolites. Thus, these genes are not directly involved in bone re-modulation.…”

Section: Cks2 Psme2 and Dhfrmentioning

confidence: 99%

Myeloma cell expression of 10 candidate genes for osteolytic bone disease. Only overexpression of DKK1 correlates with clinical bone involvement at diagnosis

et al. 2007

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SummaryOsteolytic bone disease (OBD) in multiple myeloma (MM) is caused by interactions between MM cells and the bone marrow microenvironment and is characterized by increased osteoclastic bone resorption and decreased osteoblastic bone formation. Recently, the role of osteoblast inhibition has come into focus, especially the possible role of overexpression of DKK1, an inhibitor of the Wnt signalling pathway. Further, CKS2, PSME2 and DHFR have also been reported as candidate genes for OBD. We studied the gene expression by quantitative reverse transcription polymerase chain reaction of TNFSF11 (RANKL), TNFSF11A (RANK), TNFRSF11B (OPG), CCL3 (MIP1A), CCL4 (MIP1B), PTHR1 (PTHrp), DKK1, CKS2, PSME2 and DHFR in purified, immunophenotypic FACS‐sorted plasma cells from 171 newly diagnosed MM patients, 20 patients with monoclonal gammopathy of undetermined significance and 12 controls. The gene expressions of the analysed genes were correlated with radiographically assessed OBD. Only overexpression of DKK1 was correlated to the degree of OBD. Myeloma cells did not express TNFSF11A, TNFSF11, or TNFRSF11B, and very rarely expressed CCL3 and PTHR11. CCL4, CKS2, PSME2 and DHFR were variably expressed, but the expression of these genes showed no correlation with OBD. In contrast, loss of PSME2 expression in MM plasma cells was significantly correlated with OBD.

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“…Cks2 has been implicated in the first metaphase/anaphase transition of mammalian meiosis (25). Mice lacking Cks2 are viable, but both sexes are sterile, in contrast to mice lacking Cks1 that are smaller than wild type (23).…”

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confidence: 99%

Direct Cell Cycle Regulation by the Fibroblast Growth Factor Receptor (FGFR) Kinase through Phosphorylation-dependent Release of Cks1 from FGFR Substrate 2

Zhang

Lin

Bowles

et al. 2004

Journal of Biological Chemistry

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Kip1 is a key regulatory step in activation of the cyclin E/A-Cdk complex during the G 1 /S transition of the cell cycle, the results suggest a novel mitogenic pathway whereby FGF and other growth factors that activate FRS2 directly activate cyclin-dependent kinases. The fibroblast growth factor (FGF)1 family is a ubiquitously expressed transmembrane signaling family that elicits receptor-mediated regulatory effects on cell growth, function, differentiation, and death. The FGF ligands are single polypeptides consisting of 22 genetically distinct homologues, and the FGF receptors (FGFRs) are transmembrane tyrosine kinases encoded by four homologous gene products, which complex with pericellular matrix heparan sulfates independent of the FGF ligand (1, 2). Binding of FGF ligands to FGFR-heparan sulfate complexes activates the kinase activity and transmits regulatory signals to downstream signaling mediators or targets. Accumulating reports demonstrate that FGFRs elicit diverse regulatory activities that are cell type-and FGFR-specific as well as redundant among the four FGFRs. The molecular mechanisms that would explain both specificity and redundant activities are not well understood. Two proximal substrates (FRS1 and FRS2) interact with the activated FGFR tyrosine kinases that are tyrosine-autophosphorylated. FRS1 is phospholipase C␥, which binds to phosphorylated tyrosine 766 of FGFR1, and is phosphorylated by the kinase. Activation of FRS1 is not obligatory for the mitogenic activity of FGFR1 (3, 4). However, it is important for prostate epithelial cells to acquire a mitogenic response to FGFR1 and for other cellular activities stimulated by phospholipase C␥ (5).FRS2 (also called SNT1, for suc1-associating nuclear target protein 1) is an adaptor protein that is anchored to the plasma membrane by virtue of myristoylation at the N terminus (6 -8). FRS2 interacts with the intracellular juxtamembrane sequence of the FGFR through a conserved phosphotyrosine binding (PTB) domain adjacent to the C terminus of the myristoylation consensus sequence (9, 10). The PTB domain of FRS2 is homologous to and exhibits a similar three-dimensional structure as PTB domains of several other signaling adaptor proteins, including insulin receptor substrate 1. Phosphorylation of FRS2 in response to FGF treatment is associated with the FGF mitogenic signaling (6). The C-terminal half of FRS2 has multiple candidate phosphorylation sites as well as numerous signaling molecule binding sites, which include Grb2 that recruits upstream activators of the extracellular signal-regulated kinase 1/2 in the MAP kinase pathway. Therefore, FRS2 is considered an adaptor that connects FGFR to the MAP kinase pathway (5,(11)(12)(13)(14)(15). The fact that not all FGFR signaling is tightly associated with activation of the MAP kinase pathway (16, 17) prompted us to investigate alternative and potentially more direct means by which the FGFR transmits mitogenic signals.The interaction of FRS2 with p13 suc1

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Requirement of Cks2 for the First Metaphase/Anaphase Transition of Mammalian Meiosis

Cited by 109 publications

References 17 publications

Cdc2 and Mos Regulate Emi2 Stability to Promote the Meiosis I–Meiosis II Transition

Cdc2 and Mos Regulate Emi2 Stability to Promote the Meiosis I–Meiosis II Transition

Myeloma cell expression of 10 candidate genes for osteolytic bone disease. Only overexpression of DKK1 correlates with clinical bone involvement at diagnosis

Direct Cell Cycle Regulation by the Fibroblast Growth Factor Receptor (FGFR) Kinase through Phosphorylation-dependent Release of Cks1 from FGFR Substrate 2

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