2026-06-14T03:32:28Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
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
funder
Comunidad de Madrid (España)
funder
Ministerio de Educación y Ciencia (España)
funder
Asociación Española Contra el Cáncer
funder
Ministerio de Economía y Competitividad (España)
funder
Instituto de Salud Carlos III
2017-10-30T13:15:41Z
2017-10-30T13:15:41Z
2016
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
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.
eng
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
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