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Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis.

Publication ,  Journal Article
Margolis, SS; Perry, JA; Forester, CM; Nutt, LK; Guo, Y; Jardim, MJ; Thomenius, MJ; Freel, CD; Darbandi, R; Ahn, J-H; Arroyo, JD; Wang, X-F ...
Published in: Cell
November 17, 2006

DNA-responsive checkpoints prevent cell-cycle progression following DNA damage or replication inhibition. The mitotic activator Cdc25 is suppressed by checkpoints through inhibitory phosphorylation at Ser287 (Xenopus numbering) and docking of 14-3-3. Ser287 phosphorylation is a major locus of G2/M checkpoint control, although several checkpoint-independent kinases can phosphorylate this site. We reported previously that mitotic entry requires 14-3-3 removal and Ser287 dephosphorylation. We show here that DNA-responsive checkpoints also activate PP2A/B56delta phosphatase complexes to dephosphorylate Cdc25 at a site distinct from Ser287 (T138), the phosphorylation of which is required for 14-3-3 release. However, phosphorylation of T138 is not sufficient for 14-3-3 release from Cdc25. Our data suggest that creation of a 14-3-3 "sink," consisting of phosphorylated 14-3-3 binding intermediate filament proteins, including keratins, coupled with reduced Cdc25-14-3-3 affinity, contribute to Cdc25 activation. These observations identify PP2A/B56delta as a central checkpoint effector and suggest a mechanism for controlling 14-3-3 interactions to promote mitosis.

Duke Scholars

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

November 17, 2006

Volume

127

Issue

4

Start / End Page

759 / 773

Location

United States

Related Subject Headings

  • cdc25 Phosphatases
  • Xenopus Proteins
  • Xenopus
  • Protein Subunits
  • Protein Phosphatase 2
  • Protein Kinases
  • Phosphothreonine
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • Mitosis
 

Citation

APA
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ICMJE
MLA
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Margolis, S. S., Perry, J. A., Forester, C. M., Nutt, L. K., Guo, Y., Jardim, M. J., … Kornbluth, S. (2006). Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis. Cell, 127(4), 759–773. https://doi.org/10.1016/j.cell.2006.10.035
Margolis, Seth S., Jennifer A. Perry, Craig M. Forester, Leta K. Nutt, Yanxiang Guo, Melanie J. Jardim, Michael J. Thomenius, et al. “Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis.Cell 127, no. 4 (November 17, 2006): 759–73. https://doi.org/10.1016/j.cell.2006.10.035.
Margolis SS, Perry JA, Forester CM, Nutt LK, Guo Y, Jardim MJ, et al. Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis. Cell. 2006 Nov 17;127(4):759–73.
Margolis, Seth S., et al. “Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis.Cell, vol. 127, no. 4, Nov. 2006, pp. 759–73. Pubmed, doi:10.1016/j.cell.2006.10.035.
Margolis SS, Perry JA, Forester CM, Nutt LK, Guo Y, Jardim MJ, Thomenius MJ, Freel CD, Darbandi R, Ahn J-H, Arroyo JD, Wang X-F, Shenolikar S, Nairn AC, Dunphy WG, Hahn WC, Virshup DM, Kornbluth S. Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis. Cell. 2006 Nov 17;127(4):759–773.
Journal cover image

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

November 17, 2006

Volume

127

Issue

4

Start / End Page

759 / 773

Location

United States

Related Subject Headings

  • cdc25 Phosphatases
  • Xenopus Proteins
  • Xenopus
  • Protein Subunits
  • Protein Phosphatase 2
  • Protein Kinases
  • Phosphothreonine
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • Mitosis