Protein phosphatase 2A subunit PR70 interacts with prB and mediates its dephosphorylation

Alessandra Magenta, Pasquale Fasanaro, Sveva Romani, Valeria Di Stefano, Maurizio C. Capogrossi, Fabio Martelli

Research output: Contribution to journalArticle

Abstract

The retinoblastoma tumor suppressor protein (pRb) regulates cell proliferation and differentiation via phosphorylation-sensitive interactions with specific targets. While the role of cyclin/cyclin-dependent kinase complexes in the modulation of pRb phosphorylation has been extensively studied, relatively little is known about the molecular mechanisms regulating phosphate removal by phosphatases. Protein phosphatase 2A (PP2A) is constituted by a core dimer bearing catalytic activity and one variable B regulatory subunit conferring target specificity and subcellular localization. We previously demonstrated that PP2A core dimer binds pRb and dephosphorylates pRb upon oxidative stress. In the present study, we identified a specific PP2A-B subunit, PR70, that was associated with pRb both in vitro and in vivo. PR70 overexpression caused pRb dephosphorylation; conversely, PR70 knockdown prevented both pRb dephosphorylation and DNA synthesis inhibition induced by oxidative stress. Moreover, we found that intracellular Ca2+ mobilization was necessary and sufficient to trigger pRb dephosphorylation and PP2A phosphatase activity of PR70 was Ca2+ induced. These data underline the importance of PR70-Ca2+ interaction in the signal transduction mechanisms triggered by redox imbalance and leading to pRb dephosphorylation.

Original languageEnglish
Pages (from-to)873-882
Number of pages10
JournalMolecular and Cellular Biology
Volume28
Issue number2
DOIs
Publication statusPublished - Jan 2008

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Fingerprint Dive into the research topics of 'Protein phosphatase 2A subunit PR70 interacts with prB and mediates its dephosphorylation'. Together they form a unique fingerprint.

  • Cite this