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Cited by 465

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Withdrawal of Survival Factors Results in Activation of the JNK Pathway in Neuronal Cells Leading to Fas Ligand Induction and Cell Death

Open access
Le-Niculescu, Helen, Bonfoco, Emanuela, Kasuya, Yoshitoshi, Claret, Francois-Xavier, Green, Douglas R., Karin, Michael·1999·Molecular and Cellular Biology

Abstract

The JNK pathway modulates AP-1 activity. While in some cells it may have proliferative and protective roles, in neuronal cells it is involved in apoptosis in response to stress or withdrawal of survival signals. To understand how JNK activation leads to apoptosis, we used PC12 cells and primary neuronal cultures. In PC12 cells, deliberate JNK activation is followed by induction of Fas ligand (FasL) expression and apoptosis. JNK activation detected by c-Jun phosphorylation and FasL induction are also observed after removal of either nerve growth factor from differentiated PC12 cells or KCl from primary cerebellar granule neurons (CGCs). Sequestation of FasL by incubation with a Fas-Fc decoy inhibits apoptosis in all three cases. CGCs derived from gld mice (defective in FasL) are less sensitive to apoptosis caused by KCl removal than wild-type neurons. In PC12 cells, protection is also conferred by a c-Jun mutant lacking JNK phosphoacceptor sites and a small molecule inhibitor of p38 mitogen-activated protein kinase and JNK, which inhibits FasL induction. Hence, the JNK-to-c-Jun-to-FasL pathway is an important mediator of stress-induced neuronal apoptosis.

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Crossref · 10.1128/mcb.19.1.751

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Metadata

Authors
Le-Niculescu, H., Bonfoco, E., Kasuya, Y., Claret, F.-X., Green, D. R., & Karin, M.
Venue
Molecular and Cellular Biology
Published
1999-01-01
Volume
19
Issue
1
Pages
751-763
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2144011146
Cited by
465
References
8
FWCI
20.12
Type
journal article
Language
en
Open access
green

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