Person:
Castro, Judith

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First Name
Judith
Last Name
Castro
Institution
ISCIII
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ISCIII::Unidad de Investigación en Salud Digital (UITeS)
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CNIO Organization
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2014 - 20162
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    PGA(1)-induced apoptosis involves specific activation of H-Ras and N-Ras in cellular endomembranes
    (Nature Publishing Group, 2016) Anta-Felez, Berta; Perez-Rodriguez, Andrea; Castro, Judith; Garcia-Dominguez, Carlota A; Ibiza, S; Martinez, Natalia; Dura, Lara M; Hernandez, Silvia; Gragera, Teresa; Peña-Jimenez, Daniel; Yunta, M.; Zarich-Dimitrievich, Natasha; Crespo, P.; Serrador, J. M.; Santos, E.; Munoz, A.; Oliva-Martinez, Jose Luis; Rojas-Cabañeros, Jose Maria; Comunidad de Madrid (España); Ministerio de Educación y Ciencia (España); Asociación Española Contra el Cáncer; Ministerio de Economía y Competitividad (España); Instituto de Salud Carlos III
    The cyclopentenone prostaglandin A(1) (PGA(1)) is an inducer of cell death in cancer cells. However, the mechanism that initiates this cytotoxic response remains elusive. Here we report that PGA(1) triggers apoptosis by a process that entails the specific activation of H-and N-Ras isoforms, leading to caspase activation. Cells without H- and N-Ras did not undergo apoptosis upon PGA(1) treatment; in these cells, the cellular demise was rescued by overexpression of either H-Ras or N-Ras. Consistently, the mutant H-Ras-C118-S, defective for binding PGA(1), did not produce cell death. Molecular analysis revealed a key role for the RAF-MEK-ERK signaling pathway in the apoptotic process through the induction of calpain activity and caspase-12 cleavage. We propose that PGA(1) evokes a specific physiological cell death program, through H- and N-Ras, but not K-Ras, activation at endomembranes. Our results highlight a novel mechanism that may be of potential interest for tumor treatment.
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    Publication
    Shoc2/Sur8 Protein Regulates Neurite Outgrowth
    (Public Library of Science (PLOS), 2014) Leon-Espinosa, Gonzalo; Sanchez-Ruiloba, Lucia; Perez-Rodriguez, Andrea; Gragera, Teresa; Martinez, Natalia; Hernandez, Silvia; Anta-Felez, Berta; Calero, Olga; Garcia-Dominguez, Carlota A; Dura, Lara M; Peña-Jiménez, Daniel; Castro, Judith; Zarich-Dimitrievich, Natasha; Sánchez-Gómez, Pilar; Calero, Miguel; Iglesias, Teresa; Oliva-Martinez, Jose Luis; Rojas-Cabañeros, Jose Maria; Ministerio de Educación y Ciencia (España); Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas); Comunidad de Madrid (España); Red Temática de Investigación Cooperativa en Cáncer (RTICC) (España); Asociación Española Contra el Cáncer
    The Shoc2 protein has been implicated in the positive regulation of the Ras-ERK pathway by increasing the functional binding interaction between Ras and Raf, leading to increased ERK activity. Here we found that Shoc2 overexpression induced sustained ERK phosphorylation, notably in the case of EGF stimulation, and Shoc2 knockdown inhibited ERK activation. We demonstrate that ectopic overexpression of human Shoc2 in PC12 cells significantly promotes neurite extension in the presence of EGF, a stimulus that induces proliferation rather than differentiation in these cells. Finally, Shoc2 depletion reduces both NGF-induced neurite outgrowth and ERK activation in PC12 cells. Our data indicate that Shoc2 is essential to modulate the Ras-ERK signaling outcome in cell differentiation processes involved in neurite outgrowth.