Metabolic Control of Oocyte Apoptosis Mediated by 14-3-3zeta-regulated Dephosphorylation of Caspase-2Developmental Cell (2009)
AbstractXenopus 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 DateJune, 2009
Citation InformationRafael 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)
Available at: http://works.bepress.com/rafael_fissore/16/