475C Poster - 06. Regulation of gene expression
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Jannette Rusch ¹; Chikin Kuok ²; Joe Thanintorn ¹; Yonit Tsatskis ²; Helen McNeill ¹

Affiliations:
1) Washington University St Louis School of Medicine; 2) Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada

Keywords:
c. activators/coactivators; g. Hippo

The conserved atypical cadherin fat (ft) controls cellular processes such as growth control via the Hippo pathway, planar cell polarity, and mitochondrial function, in organisms ranging from fruit flies to mammals. The intracellular domain of the Ft protein, FtICD, regulates a variety of partners to execute these functions. Our lab has found that FtICD is present in the nucleus in tissue culture cells, and we have identified both nuclear localization and nuclear export signals in Ft. Moreover, a membrane-bound version of FtICD, fused to a Gal4VP16 transactivation domain, is able to activate a reporter construct in imaginal discs, demonstrating that FtICD can be cleaved and enter the nucleus in vivo. These observations suggested that ft may have a nuclear function in addition to its cellular signaling functions. ChIP experiments on Drosophila larval tissues identified putative ft targets, including the anti-apoptotic gene, Diap1, which is also a target of the Hippo pathway. Analysis of a small fragment of the Diap1 enhancer, HRE (Hippo Response Element), in vivo suggests that FtICD can activate this element, further supporting the novel notion of a nuclear function for ft. Remarkably, FtICD ChIPs to Yorkie sites across the genome. We hypothesize that the nuclear function of Ft functions to modulate Hippo pathway activity, complementing its established function as an upstream regulator of Hippo signaling.