Apoptosis is a genetically orchestrated execution of cells that acts as a toll-gate mechanism for the development, aging, and homeostasis of the cell. In order to study cellular processes and related diseases, it is essential to understand the role of eukaryotic gene expression in the advent or evasion of cell death. Caenorhabditis elegans can be used to rapidly assess the functional impact of gene mutations to understand the dynamics of gene regulation. Sin-3, a co-repressor protein that controls gene transcription by acting as a scaffold for the multiprotein Sin-3/HDAC complex, is known to be involved in multiple cellular processes. Experimental results from our laboratory showed that
sin-3 mutation in C. elegans leads to an increase in ROS-mediated autophagy along with a sharp decline in life span. In addition,
sin-3 deletion abrogates normal development and growth in worms, resulting in cuticle defects, diminished muscle function, more susceptibility to stress, and extensive DNA damage surmounting to cell death. Therefore, Sin-3 may play a crucial role in the modulation of autophagy and longevity by regulating apoptosis. This was studied in our laboratory by an in silico analysis of the C. elegans Sin-3 protein interactome and it was found that certain Sin-3 interactors were involved in the regulation of cell death. In addition,
sin-3 mutants showed increased germline apoptosis. The major cell signaling pathways that might get upregulated in
sin-3 mutation background in C. elegans are - DNA damage response (DDR), extracellular signal-regulated protein kinase (ERK),
p38 mitogen-activated protein kinase (PMK), c-Jun N-terminal kinase (JNK) pathways. Our observations suggest the regulation of insulin/IGF-1 signaling (
daf-16), and JNK pathway (
mek-1,
jnk-1) in C. elegans by Sin-3 may play a pivotal role.