Hierarchical order of phosphorylation events commits Cdc25A to Beta-TrCP-dependent degradation

Donzelli, Maddalena; Busino, Luca; Chiesa, Massimo; Ganoth, Dvora; Hershko, Avram; Draetta, Giulio

doi:10.4161/cc.3.4.770

Cited by 32 publications

(37 citation statements)

References 17 publications

(30 reference statements)

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“…18,19,27,28 Phosphorylation of this site has been suggested to enhance subsequent phosphorylation of S82 and S88. 29 Consistent with this notion, we found that a CDC25A peptide containing phosphoS76 was more efficiently phosphorylated by NEK11 at the DSG residues compared with the peptide with unphosphorylated S76. Thus, taken together we at the G 1 /S transition is compromised in many malignant cells due to mutations in various tumor suppressor genes, including the retinoblastoma protein (pRB) and p53.…”

Section: Role Of Nek11 In the Absence Of Dna Damagesupporting

confidence: 77%

NEK11−Linking CHK1 and CDC25A in DNA damage checkpoint signaling

Sørensen

Melixetian

Klein³

et al. 2010

Cell Cycle

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Section: Role Of Nek11 In the Absence Of Dna Damagesupporting

confidence: 77%

NEK11−Linking CHK1 and CDC25A in DNA damage checkpoint signaling

Sørensen

Melixetian

Klein³

et al. 2010

Cell Cycle

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“…The consensus suggests a two-step, dual kinase model, similar to those proposed for ␤-catenin (Liu et al, 2002) and Cdc25A (Jin et al, 2003;Donzelli et al, 2004). In this model, phosphorylation of serine-149 by some unknown kinase would create a PBD binding site, which would then recruit Plk1 for phosphorylation of the consensus Plk1 target at serine-145.…”

Section: How Direct Is the Plk1 Effect On Emi1 Destruction?mentioning

confidence: 99%

Plk1 Regulates Activation of the Anaphase Promoting Complex by Phosphorylating and Triggering SCF^βTrCP-dependent Destruction of the APC Inhibitor Emi1

Hansen

Loktev

Ban

et al. 2004

MBoC

191

175

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Progression through mitosis requires activation of cyclin B/Cdk1 and its downstream targets, including Polo-like kinase and the anaphase-promoting complex (APC), the ubiquitin ligase directing degradation of cyclins A and B. Recent evidence shows that APC activation requires destruction of the APC inhibitor Emi1. In prophase, phosphorylation of Emi1 generates a D-pS-G-X-X-pS degron to recruit the SCF ␤TrCP ubiquitin ligase, causing Emi1 destruction and allowing progression beyond prometaphase, but the kinases directing this phosphorylation remain undefined. We show here that the polo-like kinase Plk1 is strictly required for Emi1 destruction and that overexpression of Plk1 is sufficient to trigger Emi1 destruction. Plk1 stimulates Emi1 phosphorylation, ␤TrCP binding, and ubiquitination in vitro and cyclin B/Cdk1 enhances these effects. Plk1 binds to Emi1 in mitosis and the two proteins colocalize on the mitotic spindle poles, suggesting that Plk1 may spatially control Emi1 destruction. These data support the hypothesis that Plk1 activates the APC by directing the SCF-dependent destruction of Emi1 in prophase.

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“…The F-box protein that targets phosphorylated CDC25A for degradation by the SCF protein complex on DNA damage and during interphase was subsequently reported to be the b-TrCP protein (Busino et al, 2003;Jin et al, 2003). A DSG binding motif within a (DSG(X) 4 S) consensus sequence present in a number of SCF substrates was identified on CDC25A, but recognition of CDC25A by b-TrCP was found to occur via a sequential phosphorylation of S76 by the CHK1 kinase and S82 by an unknown kinase (Jin et al, 2003;Donzelli et al, 2004). More recently, it was found that human and Xenopus CDC25A also contain a previously undescribed nonphosphorylated DDG motif (DDGFXD) for b-TrCP binding (Kanemori et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Differential mitotic degradation of the CDC25B phosphatase variants

et al. 2007

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CDC25 phosphatases control cell-cycle progression by dephosphorylating and activating cyclin-dependent kinases. CDC25B, one of the three members of this family in human cells, is thought to regulate initial mitotic events. CDC25B is an unstable protein whose proteasomal degradation is proposed to be controlled by b-TrCP. Here, we have investigated the regulation of CDC25B during mitosis, using time-lapse video microscopy. We found that CDC25B expression is high during early mitosis, and that its degradation occurs after the metaphase-anaphase transition and cyclin B1 destruction. We also show that CDC25B degradation after metaphase is dependent on the integrity of the KEN-box and RRKSE motifs that are located within the alternatively spliced B domain, and that the CDC25B2 splice variant, that lacks this domain, is stable during mitosis. Furthermore, we show that the N-terminal region of CDC25B, encompassing the B domain, undergoes major conformational changes during mitosis that can be monitored by intramolecular fluorescence resonance energy transfer variation of specific CDC25B biosensors. This study demonstrates that CDC25B splice variants have differential mitotic stabilities, a feature that is likely to have major consequences on the local control of cyclin-dependent kinase-cyclin activities during mitotic progression.

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Hierarchical order of phosphorylation events commits Cdc25A to Beta-TrCP-dependent degradation

Abstract: View related articles Citing articles: 19 View citing articles © L a n d e s B i o s c i e n c e 2 0 0 4. N o t f o r d i s t r i b u t i o n .

Cited by 32 publications

References 17 publications

NEK11−Linking CHK1 and CDC25A in DNA damage checkpoint signaling

NEK11−Linking CHK1 and CDC25A in DNA damage checkpoint signaling

Plk1 Regulates Activation of the Anaphase Promoting Complex by Phosphorylating and Triggering SCF^βTrCP-dependent Destruction of the APC Inhibitor Emi1

Differential mitotic degradation of the CDC25B phosphatase variants

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Hierarchical order of phosphorylation events commits Cdc25A to Beta-TrCP-dependent degradation

Abstract: View related articles Citing articles: 19 View citing articles © L a n d e s B i o s c i e n c e 2 0 0 4. N o t f o r d i s t r i b u t i o n .

Cited by 32 publications

References 17 publications

NEK11−Linking CHK1 and CDC25A in DNA damage checkpoint signaling

NEK11−Linking CHK1 and CDC25A in DNA damage checkpoint signaling

Plk1 Regulates Activation of the Anaphase Promoting Complex by Phosphorylating and Triggering SCFβTrCP-dependent Destruction of the APC Inhibitor Emi1

Differential mitotic degradation of the CDC25B phosphatase variants

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Product

Resources

About

Plk1 Regulates Activation of the Anaphase Promoting Complex by Phosphorylating and Triggering SCF^βTrCP-dependent Destruction of the APC Inhibitor Emi1