Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/28394
Title: Drosophila happyhour modulates JNK-dependent apoptosis.
Authors: Lam, D.
Shah, S.
de Castro, I.P.
Loh, S.H.Y.
Martins, L. Miguel
First Published: 15-Jul-2010
Publisher: Nature Publishing Group for Associazione Differenziamento e Morte Cellulare
Citation: Cell Death and Disease, 2010, 1, e66
Abstract: Mitogen-activated protein kinase kinase kinase kinase-3 (MAP4K3) is a Ste20 kinase family member that modulates multiple signal transduction pathways. We recently identified MAP4K3 as proapoptotic kinase using an RNA interference screening approach. In mammalian cells, MAP4K3 enhances the mitochondrial apoptosis pathway through the post-transcriptional modulation of selected proapoptotic Bcl-2 homology domain 3-only proteins. Recent data suggest that MAP4K3 mutations contribute to pancreatic cancer, which highlights the importance of studying the in vivo function of this kinase. To determine whether the cell death function is conserved in vivo and which downstream signalling pathways are involved, we generated transgenic flies expressing happyhour (hppy), the Drosophila MAP4K3 orthologue. Here, we show that the overexpression of hppy promotes caspase-dependent apoptosis and that the hypothetical kinase domain is essential for inducing cell death. In addition, we show that hppy expression triggers the activation of both the c-Jun N-terminal kinase (JNK) and target of rapamycin (TOR) signalling pathways; however, only JNK signalling is required for apoptosis. Together, our results show that hppy has a JNK-dependent proapoptotic function in Drosophila, which reinforces the hypothesis that MAP4K3 might act as tumour suppressor by regulating apoptosis in higher eukaryotes.
DOI Link: 10.1038/cddis.2010.44
eISSN: 2041-4889
Links: http://www.nature.com/cddis/journal/v1/n8/full/cddis201044a.html
http://hdl.handle.net/2381/28394
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2010, Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
Description: PMCID: PMC3032524
Appears in Collections:Published Articles, MRC Toxicology Unit

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