Loss of histone deacetylase HDAC1 induces cell death in Drosophila epithelial cells through JNK and Hippo signaling
| Autor: | Wei Du, Tianyi Zhang, Zhentao Sheng |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Embryology Programmed cell death MAP Kinase Kinase 4 Apoptosis Histone Deacetylase 1 Protein Serine-Threonine Kinases Biology Autoantigens Article 03 medical and health sciences Animals Drosophila Proteins Wings Animal Adenosine Triphosphatases Hippo signaling pathway Histone deacetylase 2 fungi Intracellular Signaling Peptides and Proteins Nuclear Proteins YAP-Signaling Proteins Mi-2/NuRD complex HDAC1 Cell biology body regions Sin3 Histone Deacetylase and Corepressor Complex Drosophila melanogaster 030104 developmental biology Imaginal Discs Hippo signaling Trans-Activators Cancer research Histone deacetylase Signal transduction Mi-2 Nucleosome Remodeling and Deacetylase Complex Signal Transduction Developmental Biology |
| Zdroj: | Mechanisms of Development. 141:4-13 |
| ISSN: | 0925-4773 |
| DOI: | 10.1016/j.mod.2016.07.001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect