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

• Published in: Apoptosis (London) Vol. 21; no. 3; pp. 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: Journal Article
• Language: English
• Published: New York Springer US 01-03-2016; Springer Nature B.V
• 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; H4K16Ac; Diap1; Hid; Mof; Reaper; Diap1 promoter; Grim; Apoptosis
• 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.