Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/5213
Title
PGA(1)-induced apoptosis involves specific activation of H-Ras and N-Ras in cellular endomembranes
Author(s)
Anta-Felez, Berta ISCIII | Perez-Rodriguez, Andrea ISCIII | Castro, Judith ISCIII | Garcia-Dominguez, Carlota A ISCIII | Ibiza, S CNIC | Martinez, Natalia ISCIII | Dura, Lara M ISCIII | Hernandez, Silvia ISCIII | Gragera, Teresa ISCIII | Peña-Jimenez, Daniel ISCIII | Yunta, M. | Zarich-Dimitrievich, Natasha ISCIII | Crespo, P. | Serrador, J. M. | Santos, E. | Munoz, A. | Oliva-Martinez, Jose Luis ISCIII | Rojas-Cabañeros, Jose Maria ISCIII
Date issued
2016
Citation
Cell Death Dis. 2016; 7(7):e2311
Language
Inglés
Document type
journal article
Abstract
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.
Subject
ENDOPLASMIC-RETICULUM STRESS | 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2) | CYCLOPENTENONE PROSTAGLANDINS | GRB2-BINDING DOMAIN | MESANGIAL CELLS | GOLGI-COMPLEX | CANCER-CELLS | DNA-BINDING | IN-VITRO | KAPPA-B
Online version
DOI
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