PMID:21364631

Citation	Brandt, B, Abou-Eladab, EF, Tiedge, M and Walzel, H (2010) Role of the JNK/c-Jun/AP-1 signaling pathway in galectin-1-induced T-cell death. Cell Death Dis 1:e23
Abstract	Galectin-1 (gal-1), an endogenous β-galactoside-binding protein, triggers T-cell death through several mechanisms including the death receptor and the mitochondrial apoptotic pathway. In this study we first show that gal-1 initiates the activation of c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase kinase 4 (MKK4), and MKK7 as upstream JNK activators in Jurkat T cells. Inhibition of JNK activation with sphingomyelinase inhibitors (20 μM desipramine, 20 μM imipramine), with the protein kinase C-δ (PKCδ) inhibitor rottlerin (10 μM), and with the specific PKCθ pseudosubstrate inhibitor (30 μM) indicates that ceramide and phosphorylation by PKCδ and PKCθ mediate gal-1-induced JNK activation. Downstream of JNK, we observed increased phosphorylation of c-Jun, enhanced activating protein-1 (AP-1) luciferase reporter, and AP-1/DNA-binding in response to gal-1. The pivotal role of the JNK/c-Jun/AP-1 pathway for gal-1-induced apoptosis was documented by reduction of DNA fragmentation after inhibition JNK by SP600125 (20 μM) or inhibition of AP-1 activation by curcumin (2 μM). Gal-1 failed to induce AP-1 activation and DNA fragmentation in CD3-deficient Jurkat 31-13 cells. In Jurkat E6.1 cells gal-1 induced a proapoptotic signal pattern as indicated by decreased antiapoptotic Bcl-2 expression, induction of proapoptotic Bad, and increased Bcl-2 phosphorylation. The results provide evidence that the JNK/c-Jun/AP-1 pathway plays a key role for T-cell death regulation in response to gal-1 stimulation.Cell Death and Disease (2010) 1, e23; doi:10.1038/cddis.2010.1; published online 4 February 2010.
Links	PubMed PMC3032336 Online version:10.1038/cddis.2010.1
Keywords	Anthracenes/pharmacology; Caspase 3/metabolism; Caspase 9/metabolism; Cell Death/drug effects; DNA/metabolism; Enzyme Activation/drug effects; Galectin 1/pharmacology; Genes, Reporter; Humans; JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases/metabolism; Jurkat Cells; Kinetics; Mitogen-Activated Protein Kinase Kinases/metabolism; Phosphorylation/drug effects; Protein Binding/drug effects; Proto-Oncogene Proteins c-jun/metabolism; Signal Transduction/drug effects; T-Lymphocytes/cytology; T-Lymphocytes/drug effects; T-Lymphocytes/enzymology; Transcription Factor AP-1/metabolism; bcl-Associated Death Protein/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:LEG1		GO:0042981: regulation of apoptosis	ECO:0000314:		P		Jurkat T lymphocytes exposed to gal-1 for 6 h underwent apoptosis as indicated by DNA fragmentation: Figure 1	complete

References

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