title: Loss of histone deacetylase HDAC1 induces cell death in Drosophila epithelial cells through JNK and Hippo signaling.
abstract: Inactivation of HDAC1 and its homolog HDAC2 or addition of HDAC inhibitors in mammalian systems induces apoptosis, cell cycle arrest, and developmental defects. Although these phenotypes have been extensively characterized, the precise underlying mechanisms remain unclear, particularly in in vivo settings. In this study, we show that inactivation of Rpd3, the only HDAC1 and HDAC2 ortholog in Drosophila, induced apoptosis and clone elimination in the developing eye and wing imaginal discs. Depletion of Rpd3 by RNAi cell-autonomously increased JNK activities and decreased activities of Yki, the nuclear effecter of Hippo signaling pathway. In addition, inhibition of JNK activities largely rescued Rpd3 RNAi-induced apoptosis, but did not affect its inhibition of Yki activities. Conversely, increasing the Yki activities largely rescued Rpd3 RNAi-induced apoptosis, but did not affect its induction of JNK activities. Furthermore, inactivation of Mi-2, a core component of the Rpd3-containing NuRD complex strongly induced JNK activities; while inactivation of Sin3A, a key component of the Rpd3-containing Sin3 complex, significantly inhibited Yki activities. Taken together, these results reveal that inactivation of Rpd3 independently regulates JNK and Yki activities and that both Hippo and JNK signaling pathways contribute to Rpd3 RNAi-induced apoptosis.
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Sheng
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA. Electronic address: wei@uchicago.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Du
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001324:Autoantigens / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development; D056284:Histone Deacetylase 1 / Q000235:genetics* / Q000378:metabolism; D060227:Imaginal Discs / Q000254:growth & development / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D048670:MAP Kinase Kinase 4 / Q000235:genetics*; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D056264:Sin3 Histone Deacetylase and Corepressor Complex / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D000251:Adenosine Triphosphatases; D001324:Autoantigens; D029721:Drosophila Proteins; D056284:Histone Deacetylase 1; D047908:Intracellular Signaling Peptides and Proteins; D048670:MAP Kinase Kinase 4; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C116095:Mi-2 protein, Drosophila; C503814:Yki protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases; C512966:HDAC1 protein, Drosophila
keywords: Apoptosis; Drosophila; Epithelial; HDAC1; Hippo; JNK; NuRD; Rpd3; Sin3; Yki