Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- 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
Published Date
- November 17, 2006
Published In
Volume / Issue
- 127 / 4
Start / End Page
- 759 - 773
PubMed ID
- 17110335
Pubmed Central ID
- PMC2789796
International Standard Serial Number (ISSN)
- 0092-8674
Digital Object Identifier (DOI)
- 10.1016/j.cell.2006.10.035
Language
- eng
Conference Location
- United States