Biochemical and genetic characterization of Caenorhabditis elegans homeodomain protein DVE-1

Abstract

Insulin/Insulin like growth factor signaling (IIS) has been implicated in several models of organismal aging. The mechanistic details of this pathway as well as its role in regulating lifespan have been established conclusively over the last two decades. Recent studies have indicated that chromatin-organizing molecules play an important role in regulating life span via IIS pathway. We have identified a role for C. elegans Homeodomain protein Defective Proventriculus (DVE-1) in regulating transcription in response to IGF signaling. Experiments reported in this document focuses on DVE-1, and its potential role in regulating the lifespan via IGF signaling pathway in C. elegans. Our results indicate that DVE-1 is expressed in all larval (L1, L2, L3, L4) and adult stages in C. elegans. The protein is expressed more in the adult stage when compared to the larval stages. The bioinformatics analysis on transcription factors that bind to 2000 bases of the 5’ UTR of dve-1 showed hits for those transcription factors, which are important players in insulin signaling indicating DVE-1 levels may be regulated by DAF-2 signaling. An interaction network was also constructed using co-expression, physical interaction and common biological functions as criteria. The interactome revealed several factors known to participate in DAF-2 signaling, further confirming the participation of DVE-1 in calorie restriction mediated regulation of lifespan. Abrogation of DVE-1 activity by using a dominant negative allele resulted in increase in the lifespan of C. elegans by 40% when compared to the control animals, confirming DVE-1 as a suppressor of DAF-2 signaling.