Cytochrome c speeds up caspase cascade activation by blocking 14-3-3 epsilon-dependent Apaf-1 inhibition
Por:
C. ELENA-REAL, A. DIAZ-QUINTANA, K. GONZALEZ-ARZOLA, A. VELAZQUEZ-CAMPOY, M. ORZAEZ, A. LOPEZ-RIVAS, S. GIL-CABALLERO, M. DE LA ROSA and I. DIAZ-MORENO
Publicada:
6 mar 2018
Resumen:
Apoptosis is a highly regulated form of programmed cell death, essential to the development and homeostasis of multicellular organisms. Cytochrome c is a central figure in the activation of the apoptotic intrinsic pathway, thereby activating the caspase cascade through its interaction with Apaf-1. Our recent studies have revealed 14-3-3 epsilon (a direct inhibitor of Apaf-1) as a cytosolic cytochrome c target. Here we explore the cytochrome c / 14-3-3 epsilon interaction and show the ability of cytochrome c to block 14-3-3 epsilon-mediated Apaf-1 inhibition, thereby unveiling a novel function for cytochrome c as an indirect activator of caspase-9/3. We have used calorimetry, NMR spectroscopy, site mutagenesis and computational calculations to provide an insight into the structural features of the cytochrome c / 14-3-3 epsilon complex. Overall, these findings suggest an additional cytochrome c-mediated mechanism to modulate apoptosome formation, shedding light onto the rigorous apoptotic regulation network.
Filiaciones:
C. ELENA-REAL:
Univ Seville, IIQ, Ctr Invest Cient Isla Cartuja CicCartuja, CSIC, Seville, Spain
A. DIAZ-QUINTANA:
Univ Seville, IIQ, Ctr Invest Cient Isla Cartuja CicCartuja, CSIC, Seville, Spain
K. GONZALEZ-ARZOLA:
Univ Seville, IIQ, Ctr Invest Cient Isla Cartuja CicCartuja, CSIC, Seville, Spain
A. VELAZQUEZ-CAMPOY:
Univ Zaragoza, Inst Biocomputat & Phys Complex Syst BIFI, Joint Unit IQFR CSIC BIFI, Zaragoza, Spain
:
Ctr Invest Principe Felipe, Valencia, Spain
A. LOPEZ-RIVAS:
Univ Seville, Univ Pablo de Olavide, CSIC, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, Seville, Spain
M. DE LA ROSA:
Univ Seville, IIQ, Ctr Invest Cient Isla Cartuja CicCartuja, CSIC, Seville, Spain
I. DIAZ-MORENO:
Univ Seville, IIQ, Ctr Invest Cient Isla Cartuja CicCartuja, CSIC, Seville, Spain
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