Role of Hippo and Ecdysone Receptor Signaling in regulation of dronc.
Karishma Sanjay Gangwani
The Hippo pathway is an evolutionarily conserved pathway that regulates organ size and tissue homeostasis in Drosophila and mammals. The pathway functions by regulating the nuclear availability of transcriptional cofactor Yorkie (Yki), mammalian YAP, which is regulated by the activity of a core kinase cascade comprising the serine threonine kinases Hippo (Hpo) and Warts (Wts) and their accessory proteins. Yki binds with transcription factors like Scalloped (Sd) or Homothorax (Hth) to regulate target genes involved in cell proliferation and survival. Downregulation of the Hpo pathway causes increased cell proliferation and overgrowth, whereas hyperactivation of this pathway leads to cell death due to activation of caspases. Caspase proteins are cysteine aspartic proteases which play essential roles in cellular signaling and development via apoptosis. We showed that the initiator caspase dronc (mammalian Caspase 9) is a transcriptional target of Yki. We found that loss of Hippo signaling leads to downregulation of dronc expression, whereas downregulation of Sd resulted in derepression of dronc expression. We also found that known binding partners of Sd like E2F and Tgi are also involved in regulating dronc expression. Earlier studies have shown that dronc expression is regulated by the Ecdysone receptor (EcR) signaling pathway and mapped a EcR regulatory element on dronc promoter. We found that depletion of EcR or its corepressors like Smrter caused de-repression of dronc expression. Overexpression of Taiman (Tai) a binding partner of EcR and Yki also derepressed dronc expression. We hypothesize that dronc expression is regulated by the Hippo and EcR signaling pathways. Here, we present our work on the regulation of dronc by the Hippo and EcR signaling pathways, and its implications on development.
Madhuri Kango-Singh, Amit Singh
Primary Advisor's Department
Stander Symposium project
"Role of Hippo and Ecdysone Receptor Signaling in regulation of dronc." (2019). Stander Symposium Projects. 1585.