Cytochrome c speeds up caspase cascade activation by blocking 14-3-3¿-dependent Apaf-1 inhibition article
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€ (a direct inhibitor of Apaf-1) as a cytosolic cytochrome c target. Here we explore the cytochrome c / 14-3-3€ interaction and show the ability of cytochrome c to block 14-3-3€-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€ complex. Overall, these findings suggest an additional cytochrome c-mediated mechanism to modulate apoptosome formation, shedding light onto the rigorous apoptotic regulation network.
Idioma: Inglés
DOI: 10.1038/s41419-018-0408-1
Año: 2018
Publicado en: Cell death & disease 9, 3 (2018), 365 [12 pp]
ISSN: 2041-4889

Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064P-BMC
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2015-71017-P-BMC
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2015-64383-P
Tipo y forma: Article (Published version)
Área (Departamento): Bioquímica y Biología Molecular (Departamento de Bioquímica y Biología Molecular y Celular)
Exportado de SIDERAL (2018-05-09-09:27:02)

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articulos > articulos-por-area > bioquimica_y_biologia_molecular

 Notice créée le 2018-05-09, modifiée le 2018-05-09

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