Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2.
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.
Nutt
Leta K
LK
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Buchakjian
Marisa R
MR
Gan
Eugene
E
Darbandi
Rashid
R
Yoon
Sook-Young
SY
Wu
Judy Q
JQ
Miyamoto
Yuko J
YJ
Gibbons
Jennifer A
JA
Gibbon
Jennifer A
JA
Andersen
Josh L
JL
Freel
Christopher D
CD
Tang
Wanli
W
He
Changli
C
Kurokawa
Manabu
M
Wang
Yongjun
Y
Margolis
Seth S
SS
Fissore
Rafael A
RA
Kornbluth
Sally
S
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
D048948:14-3-3 Proteins; D054645:Protein Phosphatase 1; D053143:Caspase 2