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

Factor impacto JCR: 5.959 (2018)
Categ. JCR: CELL BIOLOGY rank: 38 / 191 = 0.199 (2018) - Q1 - T1
Factor impacto SCIMAGO: 2.31 - Cancer Research (Q1) - Cell Biology (Q1) - Medicine (miscellaneous) (Q1) - Immunology (Q1) - Cellular and Molecular Neuroscience (Q1)

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): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)

Creative Commons You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.


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