Regulation of dronc by the Hippo pathway


Regulation of dronc by the Hippo pathway



Karishma Sanjay Gangwani, Kirti Snigdha



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 these caspases. Previous work in our lab identified the initiator caspase Dronc (mammalian Caspase 9) as a transcriptional target of Yki. Caspase proteins are cysteine aspartic proteases which play essential roles in cellular signaling, development and cell death via apoptosis or Programmed Cell Death (PCD). We found that loss of Hippo signaling leads to downregulation of dronc expression suggesting that Yki could act in co-repressor complexes to provide growth and survival cues to cells where Hippo pathway is downregulated. We hypothesize that Yki functions both as an activator and a repressor simultaneously in association with the TEAD family transcriptional factor Sd to control dronc expression. Here, we present our work on the regulation of dronc by the Hippo pathway, and its implications in organ size control, and in disease conditions like cancer.

Publication Date


Project Designation

Graduate Research

Primary Advisor

Madhuri Kango-Singh, Amit Singh

Primary Advisor's Department



Stander Symposium project

Regulation of dronc by the Hippo pathway