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

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Free keywords: INTEGRIN-LINKED KINASE; CELLS; TRANSDUCTION; EXPRESSION; DEATH; DIFFERENTIATION; ACTIVATION; ADHESIONS; COMPLEX; ADAPTERIntegrin; PINCH-1; JNK; RSU-1; Bax; Bcl-2; Apoptosis; Primitive endoderm;
 Abstract: 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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Language(s): eng - English
 Dates: 2012-11-01
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000312984300029
DOI: 10.1242/jcs.112029
 Degree: -

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Title: JOURNAL OF CELL SCIENCE
Source Genre: Journal
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Publ. Info: BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND : COMPANY OF BIOLOGISTS LTD
Pages: - Volume / Issue: 125 (21) Sequence Number: - Start / End Page: 5233 - 5240 Identifier: ISSN: 0021-9533