cdc2 phosphorylation is required for its interaction with cyclin.

Ducommun, Bernard; Brambilla, Paolo; Félix, Marie‐Anne; Franza, B. R.; Karsenti, Eric; Draetta, Giulio

doi:10.1002/j.1460-2075.1991.tb04895.x

Cited by 318 publications

(94 citation statements)

References 51 publications

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“…For example, deletion of the clathrin gene is only lethal in certain genetic backgrounds in budding yeast (Lemmon and Jones, 1987). It is also possible that while there is only a single cdc16 gene (Russell, 1989) in S.pombe, there may be multiple redundant genes in S. cerevisiae as is the case for the GI cyclins (Forsburg and Nurse, 1991 (Murray et al, 1989;Ducommun et al, 1991;Gould et al, 1991;Krek et al, 1992).…”

Section: Resultsmentioning

confidence: 99%

The S. pombe cdc16 gene is required both for maintenance of p34cdc2 kinase activity and regulation of septum formation: a link between mitosis and cytokinesis?

Fankhauser¹,

Marks²,

Reymond³

et al. 1993

The EMBO Journal

144

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In the fission yeast Schizosaccharomyces pombe, septum formation and cytokinesis are dependent upon the initiation, though not the completion of mitosis. A number of cell cycle mutants which show phenotypes consistent with a defect in the regulation of septum formation have been isolated. A mutation in the S.pombe cdc16 gene leads to the formation of multiple septa without cytokinesis, suggesting that the normal mechanisms that limit the cell to the formation of a single septum in each cycle do not operate. Mutations in the S.pombe early septation mutants cdc7, cdcll, cdc14 and cdc15 lead to the formation of elongated, multinucleate cells, as a result of S phase and mitosis continuing in the absence of cytokinesis. This suggests that in these cells, the normal mechanisms which initiate cytokinesis are defective and that they are unable to respond to this by preventing further nuclear cycles. Genetic analysis has implied that the products of some of these genes may interact with that of the cdc16 gene. To understand how the processes of septation and cytokinesis are regulated and coordinated with mitosis we are studying the early septation mutants and cdc16. In this paper, we present the cloning and analysis of the cdc16 gene. Deletion of the gene shows that it is essential for cell proliferation: spores lacking a functional cdc16 gene germinate, complete mitosis and form multiple septa without undergoing cell cleavage. Examination of the activity of p34Cdc2 kinase in the cdcl6-116 mutant shows that, after shift to the non-permissive temperature, mitotic p34M2 kinase activity decays rapidly and cells fail to respond normally to the absence of the mitotic spindle, initiating septum formation even if mitosis has not been completed. The sequence of the predicted gene product shows homology to the BUB2 gene of Saccharomyces cerevisiae. Expression of the BUB2 gene in S.pombe will rescue the cdcl6-116 mutant, but not a null allele. The cdc16 gene product may be part of a feedback mechanism preventing premature exist from mitosis by maintaining high levels of p34'd2 activity until the initiation of anaphase, thereby coordinating mitosis with septation, cytokinesis and entry into the next cycle.

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Section: Resultsmentioning

confidence: 99%

The S. pombe cdc16 gene is required both for maintenance of p34cdc2 kinase activity and regulation of septum formation: a link between mitosis and cytokinesis?

Fankhauser¹,

Marks²,

Reymond³

et al. 1993

The EMBO Journal

144

View full text Add to dashboard Cite

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“…Cyclin D1 is the regulatory subunit of the cdk4 and cdk6 holoenzyme complex, which phosphorylates and inactivates the tumor suppressor protein pRB allowing S-phase progression (Ewen et al, 1993;Matsushime et al, 1994). M-phase promoting factor (MPF), which regulates the G2-M transition, consists of the regulatory subunit cyclin B1 and the catalytic kinase cdk1 (Nurse, 1990;Ducommun et al, 1991). Expression of cyclin B1 alone can induce premature mitosis, due to the unregulated activity of cyclin B1-cdk1 kinase complexes (Hunter and Pines, 1994;Tam et al, 1995;Ghosh et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Constitutive activation of the shh–ptc1 pathway by a patched1 mutation identified in BCC

2004

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Mutations in the transmembrane receptor patched1 (ptc1) are responsible for the majority of basal cell carcinoma (BCC) cases. Many of these mutations, including ptc1-Q688X, result in premature truncation of the ptc1 protein. ptc1-Q688X has been identified in patients with both BCC and nevoid basal cell carcinoma syndrome, an inheritable disorder causing a predisposition to cancer susceptibility. Here we describe a mechanism by which ptc1-Q688X causes constitutive cellular signaling. Cells expressing ptc1-Q688X demonstrate an increase in cell cycle progression and induce cell transformation. The ptc1-Q688X mutant enhances Gli1 activity, a downstream reporter of sonic hedgehog (shh)-ptc1 signaling, independent of shh stimulation. In contrast to wild-type ptc1, ptc1-Q688X fails to associate with endogenous cyclin B1. Expression of nuclear-targeted cyclin B1 derivatives promotes Gli1-dependent transcription, which correlates temporally with cyclin B1-cdk1 kinase activity. Coexpression of wild-type ptc1 with a nuclear-targeted cyclin B1 derivative, mutated to mimic constitutive phosphorylation, dramatically decreases Gli1 activity. In addition, the coexpression of this constitutively nuclear cyclin B1 derivative with ptc1-Q688X substantially enhances foci formation. These studies therefore describe a molecular mechanism for the aberrant activity of ptc1-Q688X that includes the premature activation of the transcription factor Gli1. Oncogene (2005) 24, 902-915.

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“…Thr-161 phosphorylation is catalyzed by the Cdc2-activating kinase identified as a complex between Cdk7 (MO15), cyclin H, and MAT1 (14). This phosphorylation is necessary for Cdc2 activity (15,16). The Thr-14 and Tyr-15 residues of Cdc2 are located in the ATP-binding pocket of the kinase (17).…”

mentioning

confidence: 99%

Intra-M Phase-promoting Factor Phosphorylation of Cyclin B at the Prophase/Metaphase Transition

Borgne¹,

Østvold²,

Flament³

et al. 1999

Journal of Biological Chemistry

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in vivo phosphorylation as shown by phosphopeptide maps of in vivo and in vitro phosphorylated cyclin B. We demonstrate that Cdc2 itself is the cyclin B kinase; cyclin B phosphorylation requires Cdc2 activity both in vivo (sensitivity to vitamin K 3 , a Cdc25 inhibitor) and in vitro (copurification with Cdc2-cyclin B, requirement of Cdc2 dephosphorylation, and sensitivity to chemical inhibitors of cyclin-dependent kinases). Furthermore, cyclin B phosphorylation occurs as an intra-M phase-promoting factor reaction as shown by the following: 1) active Cdc2 is unable to phosphorylate cyclin B associated to phosphorylated Cdc2, and 2) cyclin B phosphorylation is insensitive to enzyme/substrate dilution. We conclude that, at the prophase/metaphase transition, cyclin B is mostly phosphorylated by its own associated Cdc2 subunit.Cell cycle events are regulated by the cyclin-dependent kinases (CDKs) 1 (for reviews, see Refs. 1-5). Cyclins are responsible for kinase activation, substrate specificity, and intracellular localization (6). The key regulator of the G 2 /M transition is the M phase-promoting factor (MPF), a complex constituted of the catalytic subunit p34 cdc2 (7-9) and the regulatory subunit cyclin B cdc13 (6, 10 -11). Activation of MPF at the onset of mitosis is associated with modifications of phosphorylation of its two subunits (11-13). In late prophase, Cdc2 is phosphorylated on three residues: Thr-14, Tyr-15, and Thr-161. Thr-161 phosphorylation is catalyzed by the Cdc2-activating kinase identified as a complex between Cdk7 (MO15), cyclin H, and MAT1 (14). This phosphorylation is necessary for Cdc2 activity (15, 16). The Thr-14 and Tyr-15 residues of Cdc2 are located in the ATP-binding pocket of the kinase (17). Following cyclin B binding to Cdc2 (6,12,18), Cdc2 becomes phosphorylated on Thr-14 by the Myt1 kinase (19,20) and on Tyr-15 by the Wee1/Mik1 or Myt1 kinases (20 -22). In yeast, only Tyr-15 is phosphorylated in G 2 (23). Cdc2 activation at prophase/metaphase transition requires dephosphorylation of both Thr-14 and Tyr-15. These dephosphorylations occur in two successive steps: first Thr-14 and then . The Cdc25 dual-specificity phosphatase dephosphorylates both residues (reviewed in Ref. 25). The Pyp3 tyrosine phosphatase acts on Tyr-15 in fission yeast (26). A positive feedback loop originating from Cdc2 leads to the autocatalytic amplification of the complex (27,28). This is possibly partially generated by the singly phosphorylated form of Cdc2, dephosphorylated on Thr-14/ phosphorylated on Tyr-15 (24).Simultaneously with Cdc2 dephosphorylation, cyclin B becomes phosphorylated as described in a variety of models such as yeast (6), starfish oocytes (13), sea urchin eggs (11), goldfish oocytes (29), Xenopus oocytes (30), and human cells (31). The residues phosphorylated in cyclin B 1 have been identified in Xenopus: Ser-2, Ser-94, 33). Mutational studies (29,32,33) have suggested that cyclin B phosphorylation is required neither for activity of the Cdc2 kinase, for Cdc2 binding, nor for cyclin B d...

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cdc2 phosphorylation is required for its interaction with cyclin.

Cited by 318 publications

References 51 publications

The S. pombe cdc16 gene is required both for maintenance of p34cdc2 kinase activity and regulation of septum formation: a link between mitosis and cytokinesis?

The S. pombe cdc16 gene is required both for maintenance of p34cdc2 kinase activity and regulation of septum formation: a link between mitosis and cytokinesis?

Constitutive activation of the shh–ptc1 pathway by a patched1 mutation identified in BCC

Intra-M Phase-promoting Factor Phosphorylation of Cyclin B at the Prophase/Metaphase Transition

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