Is there something else besides the proapoptotic AVPI-segment in the Smac/DIABLO protein?
Por:
Victoria-Acosta G., Martínez-Archundia M., Moreno-Vargas L., Meléndez-Zajgla J., Martínez-Ruiz G.U.
Publicada:
1 nov 2016
Categoría:
Pediatrics, Perinatology and Child Health
Resumen:
In mammals, apoptosis is the main mechanism to eliminate unwanted cells,
securing tissue homeostasis and consequently maintaining the health in
the organism. Classically, apoptosis culminates with the activation of
caspases, which are enzymes that display cysteine protease activity to
degrade specific substrates implied in essential cellular processes.
This process is highly regulated. A key regulation mechanism is mediated
by the Inhibitor of Apoptosis Proteins (IAPs) family members, which
inhibit the activated forms of caspases through physical interaction
with them. Smac/DIABLO, a mitochondrial protein that is translocated to
the cytoplasm in apoptotic conditions, derepresses the IAP-mediated
caspase inhibition through physical interaction with IAPs. The first
four amino acids (AVPI) of Smac/DIABLO mediate the interaction with IAPs
and subsequent apoptosis induction. This interaction has lead to the
creation of small molecules mimicking the AVPI segment for potential
anticancer therapy. Nevertheless, several studies have pointed out the
existence of AVPI-independent functions of Smac/DIABLO. The aim of this
review was to provide a landscape of these underestimated
AVPI-independent biological functions that have been observed using
different approaches, such as the study of endogenous splice variant
isoforms and truncated and mutated artificial proteins. (C) 2016
Hospital Infantil de Mexico Federico Gomez. Published by Masson Doyma
Mexico S.A.
Filiaciones:
Victoria-Acosta G.:
Laboratorio de Genómica Funcional del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Martínez-Archundia M.:
Laboratorio de Modelado Molecular, Diseño de Fármacos y Bioinformática, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
Moreno-Vargas L.:
Unidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México Federico Gómez, Mexico City, Mexico
Meléndez-Zajgla J.:
Laboratorio de Genómica Funcional del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Martínez-Ruiz G.U.:
Unidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México Federico Gómez, Mexico City, Mexico
Division de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
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