INVESTIGADORES
CARRIZO GARCIA Maria Elena
congresos y reuniones científicas
Título:
Biochemical and structural studies on human RILP-like protein 1. Its identification as human GOSPEL
Autor/es:
INGARAMO, MARÍA C.; ROMERO, JORGE M.; CURTINO, JUAN A.; CARRIZO, MARÍA E.
Lugar:
Mendoza
Reunión:
Congreso; XLIII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2012
Institución organizadora:
Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)
Resumen:
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
is a multi-functional protein, which is also involved in cell death, frequently
associated with oxidative and nitrosative stress. Reversible S-nitrosylation of
GAPDH facilitates its binding to the E3-ubiquitin-ligase Siah1, which possesses
a nuclear localization signal that promotes the translocation of the complex to
the nucleus resulting in a cytotoxic effect. In rats, it has recently been
described an interactor of GAPDH which interferes with the binding between
GAPDH and Siah1, preventing the apoptotic role of these proteins in the
nucleus. According to this function, the authors have designated the protein
GOSPEL (GAPDH´s Competitor Of Siah1 Protein Enhances
Life). S-nitrosylation of GOSPEL enhances GAPDH-GOSPEL binding
and the neuroprotective actions of the protein. In a
database search for GOSPEL homologues in humans, we identified a protein named
RLP1 (RILP-like protein 1), which is 93% identical to
GOSPEL. To analyze if it shares GOSPEL properties, we have prepared the
recombinant human protein and studied its capacity to be S-nitrosylated and to
bind to S-nitrosylated GAPDH. We have also made structural studies of the
protein, including the effect of oxidative stress on its oligomerization state.
Our results would suggest that the GOSPEL-mediated neuroprotective mechanism is
conserved between rodents and humans.