Drosophila MOF regulates DIAP1 and induces apoptosis in a JNK dependent pathway

• Published in: Apoptosis (London) 2016-03, Vol.21 (3), p.269-282
• Main Authors: Pushpavalli, Sreerangam N. C. V. L., Sarkar, Arpita, Ramaiah, M. Janaki, Koteswara Rao, G., Bag, Indira, Bhadra, Utpal, Pal-Bhadra, Manika
• Format: Article
• Language: English
• Subjects: Acetylation; Animals; Apoptosis - genetics; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cancer Research; Caspases - metabolism; Cell Biology; Drosophila; Drosophila melanogaster - cytology; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Eye - growth & development; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; Histone Acetyltransferases - genetics; Histone Acetyltransferases - metabolism; Histones - metabolism; Imaginal Discs - abnormalities; Imaginal Discs - cytology; Inhibitor of Apoptosis Proteins - genetics; Larva; Larvae; Male; MAP Kinase Kinase Kinases - genetics; MAP Kinase Kinase Kinases - metabolism; MAP Kinase Signaling System - physiology; Neuropeptides - genetics; Neuropeptides - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oncology; Original Paper; Phenotype; Promoter Regions, Genetic; RNA Interference; Transcription, Genetic; Up-Regulation; Virology
• ISSN: 1360-8185; 1573-675X
• DOI: 10.1007/s10495-015-1206-1

Histone modulations have been implicated in various cellular and developmental processes where in Drosophila Mof is involved in acetylation of H4K16. Reduction in the size of larval imaginal discs is observed in the null mutants of mof with increased apoptosis. Deficiency involving Hid , Reaper and Grim [H99] alleviated mof RNAi induced apoptosis in the eye discs. mof RNAi induced apoptosis leads to activation of caspases which is suppressed by over expression of caspase inhibitors like P35 and Diap1 clearly depicting the role of caspases in programmed cell death. Also apoptosis induced by knockdown of mof is rescued by JNK mutants of bsk and tak1 indicating the role of JNK in mof RNAi induced apoptosis. The adult eye ablation phenotype produced by ectopic expression of Hid , Rpr and Grim , was restored by over expression of Mof . Accumulation of Mof at the Diap1 promoter 800 bp upstream of the transcription start site in wild type larvae is significantly higher (up to twofolds) compared to mof 1 mutants. This enrichment coincides with modification of histone H4K16Ac indicating an induction of direct transcriptional up regulation of Diap1 by Mof. Based on these results we propose that apoptosis triggered by mof RNAi proceeds through a caspase-dependent and JNK mediated pathway.