Transcriptional regulation of dronc by the Hippo pathway.
Karishma S Gangwani, Kirti Snigdha
The growth regulatory Hippo pathway maintains tissue homeostasis by tightly regulating cell proliferation and cell death. This key pathway is conserved between humans and fruit flies (Drosophila melanogaster), and misexpression of this pathway is linked to cancer. The core components of the pathway include two kinases Hippo (Hpo) and its target Warts (Wts) and the transcriptional co-activator Yorkie (Yki). When the pathway is active, Hippo (Hpo) along with Wts bring about phosphorylation of Yki which leads to cell death. Yki acts in an activator complex by associating with Scalloped (Sd) to regulate target genes. Inactivation of hpo leads to overgrowth due to activation of cell cycle and cell proliferation genes such as Cyclin E, A, B, D, and diap1; and downregulation of caspases of the apoptotic pathway like dronc and drice which ensures that cells/tissues overproliferate on pathway downregulation. These Yki mediated regulatory interactions are thought to promote tumor growth. Previous work from our lab has shown that the Hippo pathway transcriptionally downregulates dronc- this is an important but underexplored aspect of Hippo signaling as till date dronc is the only negatively regulated transcriptional target of the Hippo pathway. To induce cell death, Dronc activates caspase-3 (Drice) that leads to formation of the apoptosome complex. When Yki levels are low inside the nucleus there is an increase of Dronc expression and vice versa, however, it is unknown if Yki directly regulates dronc expression during Hippo signaling. We hypothesize that Yki functions both as an activator and a repressor simultaneously. To test this, we will express transgenic constructs expressing different sequences of the Dronc promoter to find which sequences are required for Yki mediated dronc repression. We are also investigating the transcription factors/repressors that may associate with Yki to mediate its repressive activity. Here we present our findings from these studies.
Graduate Research - Graduate
Madhuri Kango-Singh, Amit Singh
Primary Advisor's Department
Stander Symposium poster
"Transcriptional regulation of dronc by the Hippo pathway." (2017). Stander Symposium Posters. 1041.