Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability.

Research output: Contribution to journal › Journal article › Research › peer-review

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Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability. / Mailand, Niels; Podtelejnikov, Alexandre V; Groth, Anja; Mann, Matthias; Bartek, Jiri; Lukas, Jiri.

In: EMBO Journal, Vol. 21, No. 21, 2002, p. 5911-20.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Mailand, N, Podtelejnikov, AV, Groth, A, Mann, M, Bartek, J & Lukas, J 2002, 'Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability.', EMBO Journal, vol. 21, no. 21, pp. 5911-20. https://doi.org/10.1093/emboj/cdf567

APA

Mailand, N., Podtelejnikov, A. V., Groth, A., Mann, M., Bartek, J., & Lukas, J. (2002). Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability. EMBO Journal, 21(21), 5911-20. https://doi.org/10.1093/emboj/cdf567

Vancouver

Mailand N, Podtelejnikov AV, Groth A, Mann M, Bartek J, Lukas J. Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability. EMBO Journal. 2002;21(21):5911-20. https://doi.org/10.1093/emboj/cdf567

Author

Mailand, Niels ; Podtelejnikov, Alexandre V ; Groth, Anja ; Mann, Matthias ; Bartek, Jiri ; Lukas, Jiri. / Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability. In: EMBO Journal. 2002 ; Vol. 21, No. 21. pp. 5911-20.

Bibtex

@article{7550bf00518111dd8d9f000ea68e967b,
title = "Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability.",
abstract = "DNA replication in higher eukaryotes requires activation of a Cdk2 kinase by Cdc25A, a labile phosphatase subject to further destabilization upon genotoxic stress. We describe a distinct, markedly stable form of Cdc25A, which plays a previously unrecognized role in mitosis. Mitotic stabilization of Cdc25A reflects its phosphorylation on Ser17 and Ser115 by cyclin B-Cdk1, modifications required to uncouple Cdc25A from its ubiquitin-proteasome-mediated turnover. Cdc25A binds and activates cyclin B-Cdk1, accelerates cell division when overexpressed, and its downregulation by RNA interference (RNAi) delays mitotic entry. DNA damage-induced G(2) arrest, in contrast, is accompanied by proteasome-dependent destruction of Cdc25A, and ectopic Cdc25A abrogates the G(2) checkpoint. Thus, phosphorylation-mediated switches among three differentially stable forms ensure distinct thresholds, and thereby distinct roles for Cdc25A in multiple cell cycle transitions and checkpoints.",
author = "Niels Mailand and Podtelejnikov, {Alexandre V} and Anja Groth and Matthias Mann and Jiri Bartek and Jiri Lukas",
note = "Keywords: Amino Acid Sequence; Animals; CDC2 Protein Kinase; Cyclin B; DNA Damage; Enzyme Stability; G2 Phase; Humans; Mitosis; Molecular Sequence Data; Phosphorylation; Serine; Ubiquitin; cdc25 Phosphatases",
year = "2002",
doi = "10.1093/emboj/cdf567",
language = "English",
volume = "21",
pages = "5911--20",
journal = "E M B O Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "21",

}

RIS

TY - JOUR

T1 - Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability.

AU - Mailand, Niels

AU - Podtelejnikov, Alexandre V

AU - Groth, Anja

AU - Mann, Matthias

AU - Bartek, Jiri

AU - Lukas, Jiri

N1 - Keywords: Amino Acid Sequence; Animals; CDC2 Protein Kinase; Cyclin B; DNA Damage; Enzyme Stability; G2 Phase; Humans; Mitosis; Molecular Sequence Data; Phosphorylation; Serine; Ubiquitin; cdc25 Phosphatases

PY - 2002

Y1 - 2002

N2 - DNA replication in higher eukaryotes requires activation of a Cdk2 kinase by Cdc25A, a labile phosphatase subject to further destabilization upon genotoxic stress. We describe a distinct, markedly stable form of Cdc25A, which plays a previously unrecognized role in mitosis. Mitotic stabilization of Cdc25A reflects its phosphorylation on Ser17 and Ser115 by cyclin B-Cdk1, modifications required to uncouple Cdc25A from its ubiquitin-proteasome-mediated turnover. Cdc25A binds and activates cyclin B-Cdk1, accelerates cell division when overexpressed, and its downregulation by RNA interference (RNAi) delays mitotic entry. DNA damage-induced G(2) arrest, in contrast, is accompanied by proteasome-dependent destruction of Cdc25A, and ectopic Cdc25A abrogates the G(2) checkpoint. Thus, phosphorylation-mediated switches among three differentially stable forms ensure distinct thresholds, and thereby distinct roles for Cdc25A in multiple cell cycle transitions and checkpoints.

AB - DNA replication in higher eukaryotes requires activation of a Cdk2 kinase by Cdc25A, a labile phosphatase subject to further destabilization upon genotoxic stress. We describe a distinct, markedly stable form of Cdc25A, which plays a previously unrecognized role in mitosis. Mitotic stabilization of Cdc25A reflects its phosphorylation on Ser17 and Ser115 by cyclin B-Cdk1, modifications required to uncouple Cdc25A from its ubiquitin-proteasome-mediated turnover. Cdc25A binds and activates cyclin B-Cdk1, accelerates cell division when overexpressed, and its downregulation by RNA interference (RNAi) delays mitotic entry. DNA damage-induced G(2) arrest, in contrast, is accompanied by proteasome-dependent destruction of Cdc25A, and ectopic Cdc25A abrogates the G(2) checkpoint. Thus, phosphorylation-mediated switches among three differentially stable forms ensure distinct thresholds, and thereby distinct roles for Cdc25A in multiple cell cycle transitions and checkpoints.

U2 - 10.1093/emboj/cdf567

DO - 10.1093/emboj/cdf567

M3 - Journal article

C2 - 12411508

VL - 21

SP - 5911

EP - 5920

JO - E M B O Journal

JF - E M B O Journal

SN - 0261-4189

IS - 21

ER -

ID: 5014001