Reference Report

Reference
Citation	Lam, D., Shah, S., de Castro, I.P., Loh, S.H., Martins, L.M. (2010). Drosophila happyhour modulates JNK-dependent apoptosis. Cell Death Dis. 1(8): e66. (Export to RIS)
FlyBase ID	FBrf0213175
Publication Type	Research paper
PubMed ID	21364671
PubMed 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	10.1038/cddis.2010.44
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Cell Death Dis.
Title	Cell death & disease
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ISBN/ISSN	2041-4889
Data from Reference
Alleles (13)
	Avic\GFP^{S65T.Scer\UAS} BacA\p35^Scer\UAS.cHa bsk^DN.Scer\UAS Buffy^Scer\UAS.cQa Ecol\lacZ^puc-E69 gig^Scer\UAS.cTa hppy^{K55E.Scer\UAS} hppy^Scer\UAS.cLa puc^EY09772 Scer\GAL4^da.G32 Scer\GAL4^e22c Thor^TA.Scer\UAS Tsc1^Scer\UAS.cTa
Constructs (10)
	P{GAL4-da.G32} P{UAS-bsk.DN} P{UAS-Buffy.Q} P{UAS-GFP.S65T} P{UAS-gig.T} P{UAS-hppy.KD} P{UAS-hppy.L} P{UAS-p35.H} P{UAS-Thor.TA} P{UAS-Tsc1.T}
Genes (11)
	Avic\GFP BacA\p35 bsk Buffy Ecol\lacZ gig hppy puc Scer\GAL4 Thor Tsc1
Insertions (5)
	P{A92}puc^E69 P{en2.4-GAL4}e22c P{EPgy2}puc^EY09772 P{UAS-hppy.L}4M P{UAS-hppy.L}7F
Natural transposons (1)
	P-element