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Metabolic Control of Oocyte Apoptosis Mediated by 14-3-3zeta-regulated Dephosphorylation of Caspase-2
Developmental Cell (2009)
  • Rafael Fissore, University of Massachusetts - Amherst
  • L.K. Nutt
  • M.R. Buchakjian
  • E. Gan
  • R. Darbandi
  • S.Y. Yoon
  • J.Q. Wu
  • Y.J. Miyamoto
  • J.A. Gibbons
  • J.L. Andersen
  • C.D. Freel
  • W. Tang
  • C. He
  • M. Kurokawa
  • Y. Wang
  • S.S. Margolis
  • S. Kornbluth
Xenopus oocyte death is partly controlled by the apoptotic initiator caspase-2 (C2). We reported previously that oocyte nutrient depletion activates C2 upstream of mitochondrial cytochrome c release. Conversely, nutrient-replete oocytes inhibit C2 via S135 phosphorylation catalyzed by calcium/calmodulin-dependent protein kinase II. We now show that C2 phosphorylated at S135 binds 14-3-3zeta, thus preventing C2 dephosphorylation. Moreover, we determined that S135 dephosphorylation is catalyzed by protein phosphatase-1 (PP1), which directly binds C2. Although C2 dephosphorylation is responsive to metabolism, neither PP1 activity nor binding is metabolically regulated. Rather, release of 14-3-3zeta from C2 is controlled by metabolism and allows for C2 dephosphorylation. Accordingly, a C2 mutant unable to bind 14-3-3zeta is highly susceptible to dephosphorylation. Although this mechanism was initially established in Xenopus, we now demonstrate similar control of murine C2 by phosphorylation and 14-3-3 binding in mouse eggs. These findings provide an unexpected evolutionary link between 14-3-3 and metabolism in oocyte death.
Publication Date
June, 2009
Citation Information
Rafael Fissore, L.K. Nutt, M.R. Buchakjian, E. Gan, et al.. "Metabolic Control of Oocyte Apoptosis Mediated by 14-3-3zeta-regulated Dephosphorylation of Caspase-2" Developmental Cell Vol. 16 Iss. 6 (2009)
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