Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2.

ABSTRACT: 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 muta

SUBMITTER: Nutt LK 

PROVIDER: S-EPMC2698816 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature