Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/80355
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | JNK activation is critical for Aplidin™-induced apoptosis |
Autor: | Cuadrado, Ana CSIC ORCID; González-Santiago, L. CSIC; Suárez, Yajaira; Martínez, Teresa CSIC; Muñoz Terol, Alberto CSIC ORCID | Fecha de publicación: | 2004 | Editor: | Nature Publishing Group | Citación: | Oncogene 23(27): 4673-4680 (2004) | Resumen: | Aplidin is an antitumor drug that induces apoptosis and activates EGFR, Src, JNK and p38MAPK. Here, we show that Aplidin induces c-JUN, JUN B, JUN D, c-FOS, FRA-1 and FOS B genes of the activator-protein (AP)-1 family, and also p65/RELA, a major component of nuclear factor-kappa B (NF-kappaB). Concordantly, Aplidin increases AP-1 and NF-kappaB activity. c-FOS induction depends on EGFR, Src and JNK/p38MAPK. In contrast, induction of c-JUN does not require EGFR activity and p65/RELA induction is only partially dependent on these kinases. We used several genetically deficient cells to identify the critical target of Aplidin. Mouse embryo fibroblasts (MEFs) deficient for src, yes and fyn, and those lacking all p38MAPK isoforms displayed normal Aplidin sensitivity (IC50=12 nM). In contrast, MEFs lacking jnk1 and jnk2, which do not express any JNK isoform, were much less sensitive (IC50>500 nM). Furthermore, cells lacking c-jun or expressing a c-Jun protein in which JNK targets Ser(63/73) were mutated (c-JunAA) showed intermediate sensitivity (IC50=60 nM). Additionally, Aplidin has higher cytotoxic activity against proliferating than quiescent cells, which is reflected in higher JNK activation. We conclude that phosphorylation by JNK of c-Jun and additional substrate(s) is crucial for Aplidin activity. | URI: | http://hdl.handle.net/10261/80355 | DOI: | 10.1038/sj.onc.1207636 | Identificadores: | doi: 10.1038/sj.onc.1207636 issn: 0950-9232 e-issn: 1476-5594 |
Aparece en las colecciones: | (IIBM) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
65
checked on 28-abr-2024
WEB OF SCIENCETM
Citations
62
checked on 22-feb-2024
Page view(s)
298
checked on 30-abr-2024
Download(s)
79
checked on 30-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.