title: 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 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.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Leta K
authors.initials: LK
authors.lastname: Nutt
authors.forename: Marisa R
authors.initials: MR
authors.lastname: Buchakjian
authors.forename: Eugene
authors.initials: E
authors.lastname: Gan
authors.forename: Rashid
authors.initials: R
authors.lastname: Darbandi
authors.forename: Sook-Young
authors.initials: SY
authors.lastname: Yoon
authors.forename: Judy Q
authors.initials: JQ
authors.lastname: Wu
authors.forename: Yuko J
authors.initials: YJ
authors.lastname: Miyamoto
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Gibbons
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Gibbon
authors.forename: Josh L
authors.initials: JL
authors.lastname: Andersen
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Freel
authors.forename: Wanli
authors.initials: W
authors.lastname: Tang
authors.forename: Changli
authors.initials: C
authors.lastname: He
authors.forename: Manabu
authors.initials: M
authors.lastname: Kurokawa
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.forename: Seth S
authors.initials: SS
authors.lastname: Margolis
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Fissore
authors.forename: Sally
authors.initials: S
authors.lastname: Kornbluth
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D053143:Caspase 2 / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D051379:Mice; D009865:Oocytes / Q000166:cytology* / Q000201:enzymology*; D010766:Phosphorylation; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D014981:Xenopus
chemical_list: D048948:14-3-3 Proteins; D054645:Protein Phosphatase 1; D053143:Caspase 2