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XB-ART-34885
Cell 2006 Nov 17;1274:759-73. doi: 10.1016/j.cell.2006.10.035.
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Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis.

Margolis SS , Perry JA , Forester CM , Nutt LK , Guo Y , Jardim MJ , Thomenius MJ , Freel CD , Darbandi R , Ahn JH , Arroyo JD , Wang XF , Shenolikar S , Nairn AC , Dunphy WG , Hahn WC , Virshup DM , Kornbluth S .


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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.

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Species referenced: Xenopus
Genes referenced: cdc25c ptpa rasgrf1

References [+] :
Clarke, Dephosphorylation of cdc25-C by a type-2A protein phosphatase: specific regulation during the cell cycle in Xenopus egg extracts. 1993, Pubmed, Xenbase