RT Journal Article
T1 Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent Apaf-1 inhibition.
A1 Elena-Real, Carlos A
A1 Díaz-Quintana, Antonio
A1 González-Arzola, Katiuska
A1 Velázquez-Campoy, Adrián
A1 Orzáez, Mar
A1 López-Rivas, Abelardo
A1 Gil-Caballero, Sergio
A1 De la Rosa, Miguel Á
A1 Díaz-Moreno, Irene
AB 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 14-3-3ε (a direct inhibitor of Apaf-1) as a cytosolic cytochrome c target. Here we explore the cytochrome c / 14-3-3ε interaction and show the ability of cytochrome c to block 14-3-3ε-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 / 14-3-3ε complex. Overall, these findings suggest an additional cytochrome c-mediated mechanism to modulate apoptosome formation, shedding light onto the rigorous apoptotic regulation network.
YR 2018
FD 2018-03-06
LK http://hdl.handle.net/10668/12211
UL http://hdl.handle.net/10668/12211
LA en
DS RISalud
RD Apr 5, 2025