Protein phosphatase 2A is targeted to cell division control protein 6 by a calcium-binding regulatory subunit

Anthony J. Davis, Zhen Yan, Bobbie Martinez, Marc C. Mumby

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The cell division control protein 6 (Cdc6) is essential for formation of pre-replication complexes at origins of DNA replication. Phosphorylation of Cdc6 by cyclin-dependent kinases inhibits ubiquitination of Cdc6 by APC/C cdh1 and degradation by the proteasome. Experiments described here show that the PR70 member of the PPP2R3 family of regulatory subunits targets protein phosphatase 2A (PP2A) to Cdc6. Interaction with Cdc6 is mediated by residues within the C terminus of PR70, whereas interaction with PP2A requires N-terminal sequences conserved within the PPP2R3 family. Two functional EF-hand calcium-binding motifs mediate a calcium-enhanced interaction of PR70 with PP2A. Calcium has no effect on the interaction of PR70 with Cdc6 but enhances the association of PP2A with Cdc6 through its effects on PR70. Knockdown of PR70 by RNA interference results in an accumulation of endogenous and expressed Cdc6 protein that is dependent on the cyclin-dependent protein kinase phosphorylation sites on Cdc6. Knockdown of PR70 also causes G1 arrest, suggesting that PR70 function is critical for progression into S phase. These observations indicate that PP2A can be targeted in a calcium-regulated manner to Cdc6 via the PR70 subunit, where it plays a role in regulating protein phosphorylation and stability.

Original languageEnglish (US)
Pages (from-to)16104-16114
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number23
DOIs
StatePublished - Jun 6 2008

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Protein Phosphatase 2
Cell Division
Cells
Calcium
Proteins
Phosphorylation
Cyclin-Dependent Kinases
EF Hand Motifs
Cyclin-Dependent Kinase 6
Replication Origin
Conserved Sequence
Protein Stability
Ubiquitination
Proteasome Endopeptidase Complex
RNA Interference
DNA Replication
S Phase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Protein phosphatase 2A is targeted to cell division control protein 6 by a calcium-binding regulatory subunit. / Davis, Anthony J.; Yan, Zhen; Martinez, Bobbie; Mumby, Marc C.

In: Journal of Biological Chemistry, Vol. 283, No. 23, 06.06.2008, p. 16104-16114.

Research output: Contribution to journalArticle

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