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A role for PP1 in the Cdc2/Cyclin B-mediated positive feedback activation of Cdc25.

Publication ,  Journal Article
Margolis, SS; Perry, JA; Weitzel, DH; Freel, CD; Yoshida, M; Haystead, TA; Kornbluth, S
Published in: Mol Biol Cell
April 2006

The Cdc25 phosphatase promotes entry into mitosis through the removal of inhibitory phosphorylations on the Cdc2 subunit of the Cdc2/CyclinB complex. During interphase, or after DNA damage, Cdc25 is suppressed by phosphorylation at Ser287 (Xenopus numbering; Ser216 of human Cdc25C) and subsequent binding of the small acidic protein, 14-3-3. As reported recently, at the time of mitotic entry, 14-3-3 protein is removed from Cdc25 and S287 is dephosphorylated by protein phosphatase 1 (PP1). After the initial activation of Cdc25 and consequent derepression of Cdc2/CyclinB, Cdc25 is further activated through a Cdc2-catalyzed positive feedback loop. Although the existence of such a loop has been appreciated for some time, the molecular mechanism for this activation has not been described. We report here that phosphorylation of S285 by Cdc2 greatly enhances recruitment of PP1 to Cdc25, thereby accelerating S287 dephosphorylation and mitotic entry. Moreover, we show that two other previously reported sites of Cdc2-catalyzed phosphorylation on Cdc25 are required for maximal biological activity of Cdc25, but they do not contribute to PP1 regulation and do not act solely through controlling S287 phosphorylation. Therefore, multiple mechanisms, including enhanced recruitment of PP1, are used to promote full activation of Cdc25 at the time of mitotic entry.

Duke Scholars

Published In

Mol Biol Cell

DOI

ISSN

1059-1524

Publication Date

April 2006

Volume

17

Issue

4

Start / End Page

1779 / 1789

Location

United States

Related Subject Headings

  • cdc25 Phosphatases
  • Xenopus
  • Threonine
  • Serine
  • Protein Phosphatase 1
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • Mutation
  • Mitosis
  • Feedback, Physiological
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Margolis, S. S., Perry, J. A., Weitzel, D. H., Freel, C. D., Yoshida, M., Haystead, T. A., & Kornbluth, S. (2006). A role for PP1 in the Cdc2/Cyclin B-mediated positive feedback activation of Cdc25. Mol Biol Cell, 17(4), 1779–1789. https://doi.org/10.1091/mbc.e05-08-0751
Margolis, Seth S., Jennifer A. Perry, Douglas H. Weitzel, Christopher D. Freel, Minoru Yoshida, Timothy A. Haystead, and Sally Kornbluth. “A role for PP1 in the Cdc2/Cyclin B-mediated positive feedback activation of Cdc25.Mol Biol Cell 17, no. 4 (April 2006): 1779–89. https://doi.org/10.1091/mbc.e05-08-0751.
Margolis SS, Perry JA, Weitzel DH, Freel CD, Yoshida M, Haystead TA, et al. A role for PP1 in the Cdc2/Cyclin B-mediated positive feedback activation of Cdc25. Mol Biol Cell. 2006 Apr;17(4):1779–89.
Margolis, Seth S., et al. “A role for PP1 in the Cdc2/Cyclin B-mediated positive feedback activation of Cdc25.Mol Biol Cell, vol. 17, no. 4, Apr. 2006, pp. 1779–89. Pubmed, doi:10.1091/mbc.e05-08-0751.
Margolis SS, Perry JA, Weitzel DH, Freel CD, Yoshida M, Haystead TA, Kornbluth S. A role for PP1 in the Cdc2/Cyclin B-mediated positive feedback activation of Cdc25. Mol Biol Cell. 2006 Apr;17(4):1779–1789.

Published In

Mol Biol Cell

DOI

ISSN

1059-1524

Publication Date

April 2006

Volume

17

Issue

4

Start / End Page

1779 / 1789

Location

United States

Related Subject Headings

  • cdc25 Phosphatases
  • Xenopus
  • Threonine
  • Serine
  • Protein Phosphatase 1
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • Mutation
  • Mitosis
  • Feedback, Physiological