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  PINCH-1 promotes Bcl-2-dependent survival signalling and inhibits JNK-mediated apoptosis in the primitive endoderm

Montanez, E., Karaköse, E., Tischner, D., Villunger, A., & Fässler, R. (2012). PINCH-1 promotes Bcl-2-dependent survival signalling and inhibits JNK-mediated apoptosis in the primitive endoderm. JOURNAL OF CELL SCIENCE, 125(21), 5233-5240. doi:10.1242/jcs.112029.

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 Urheber:
Montanez, Eloi1, Autor           
Karaköse, Esra1, Autor           
Tischner, Denise2, Autor
Villunger, Andreas2, Autor
Fässler, Reinhard1, Autor           
Affiliations:
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              
2external, ou_persistent22              

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Schlagwörter: INTEGRIN-LINKED KINASE; CELLS; TRANSDUCTION; EXPRESSION; DEATH; DIFFERENTIATION; ACTIVATION; ADHESIONS; COMPLEX; ADAPTERIntegrin; PINCH-1; JNK; RSU-1; Bax; Bcl-2; Apoptosis; Primitive endoderm;
 Zusammenfassung: The focal adhesion (FA) protein PINCH-1 is required for the survival of primitive endoderm (PrE) cells. How PINCH-1 regulates this fundamental process is not known. Here, we use embryoid bodies (EBs) and isolated EB-derived PrE cells to investigate the mechanisms by which PINCH-1 promotes PrE survival. We report that loss of PINCH-1 in PrE cells leads to a sustained activity of JNK and the proapoptotic factor Bax. Mechanistically, the sustained JNK activation was due to diminished levels of the JNK inhibitory factor Ras suppressor protein-1 (RSU-1), whose stability was severely reduced upon loss of PINCH-1. Chemical inhibition of JNK attenuated apoptosis of PrE cells but failed to reduce Bax activity. The increased Bax activity was associated with reduced integrin signalling and diminished Bcl-2 levels, which were shown to inhibit Bax. Altogether our findings show that PINCH-1 is a pro-survival factor that prevents apoptosis of PrE cells by modulating two independent signalling pathways; PINCH-1 inhibits JNK-mediated apoptosis by stabilising the PINCH-1 binding protein RSU-1 and promotes Bcl-2-dependent pro-survival signalling downstream of integrins.

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Sprache(n): eng - English
 Datum: 2012-11-01
 Publikationsstatus: Erschienen
 Seiten: 8
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: ISI: 000312984300029
DOI: 10.1242/jcs.112029
 Art des Abschluß: -

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Titel: JOURNAL OF CELL SCIENCE
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND : COMPANY OF BIOLOGISTS LTD
Seiten: - Band / Heft: 125 (21) Artikelnummer: - Start- / Endseite: 5233 - 5240 Identifikator: ISSN: 0021-9533