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

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Abstract

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 Diap1clearly 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.

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Acknowledgments

This work has been supported by Department of Biotechnology to MPB [GAP 0362] and UB. The authors thank Prof. John C. Lucchesi for fly stocks. AS, GKR thank UGC for their fellowship and IB thank CSIR for her postdoctoral fellowship. All the authors thank P. Devender for culturing and maintaining the Drosophila stocks. Our thanks to Hemalatha for help in formatting the work.

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    1. Centre for Chemical Biology, Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India

      Arpita Sarkar, M. Janaki Ramaiah, G. Koteswara Rao, Indira Bag & Manika Pal-Bhadra

    2. Agricultural Research Station, Prof. Jayashankar Telangana State Agricultural University, Tandur, 501141, Telangana, India

      Sreerangam N. C. V. L. Pushpavalli

    3. School of Chemical and Biotechnology (SCBT), SASTRA University, Tirumalaisamudram, Thanjavur, Tamil Nadu, 613401, India

      M. Janaki Ramaiah

    4. Functional Genomics and Gene Silencing Group, Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500007, India

      Indira Bag & Utpal Bhadra

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    Sreerangam N. C. V. L. Pushpavalli, Arpita Sarkar and M. Janaki Ramaiah have contributed equally to this work.

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    Pushpavalli, S.N.C.V.L., Sarkar, A., Ramaiah, M.J. et al. Drosophila MOF regulates DIAP1 and induces apoptosis in a JNK dependent pathway. Apoptosis 21, 269–282 (2016). https://doi.org/10.1007/s10495-015-1206-1

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