2026-06-14T03:33:35Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/52132025-05-08T12:15:52Zcom_20.500.12105_19604com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_19605col_20.500.12105_19617

00925njm 22002777a 4500 dc Anta-Felez, Berta author Perez-Rodriguez, Andrea author Castro, Judith author Garcia-Dominguez, Carlota A author Ibiza, S author Martinez, Natalia author Dura, Lara M author Hernandez, Silvia author Gragera, Teresa author Peña-Jimenez, Daniel author Yunta, M. author Zarich-Dimitrievich, Natasha author Crespo, P. author Serrador, J. M. author Santos, E author Munoz, A. author Oliva-Martinez, Jose Luis author Rojas-Cabañeros, Jose Maria author 2016 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. Cell Death Dis. 2016; 7(7):e2311 10.1038/cddis.2016.219 2041-4889 Cell Death & Disease 27468687 http://hdl.handle.net/20.500.12105/5213 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 PGA(1)-induced apoptosis involves specific activation of H-Ras and N-Ras in cellular endomembranes