TY - JOUR TI - Nerfin-1 represses transcriptional output of Hippo signaling in cell competition AU - Guo, Pengfei AU - Lee, Chang-Hyun AU - Lei, Huiyan AU - Zheng, Yonggang AU - Pulgar Prieto, Katiuska Daniela AU - Pan, Duojia A2 - Stainier, Didier Y A2 - Banerjee, Utpal A2 - Moreno, Eduardo A2 - Guan, Kun-Liang A2 - Halder, Georg VL - 8 PY - 2019 DA - 2019/03/22 SP - e38843 C1 - eLife 2019;8:e38843 DO - 10.7554/eLife.38843 UR - https://doi.org/10.7554/eLife.38843 AB - The Hippo tumor suppressor pathway regulates tissue growth in Drosophila by restricting the activity of the transcriptional coactivator Yorkie (Yki), which normally complexes with the TEF/TEAD family DNA-binding transcription factor Scalloped (Sd) to drive the expression of growth-promoting genes. Given its pivotal role as a central hub in mediating the transcriptional output of Hippo signaling, there is great interest in understanding the molecular regulation of the Sd-Yki complex. In this study, we identify Nerfin-1 as a transcriptional repressor that antagonizes the activity of the Sd-Yki complex by binding to the TEA DNA-binding domain of Sd. Consistent with its biochemical function, ectopic expression of Nerfin-1 results in tissue undergrowth in an Sd-dependent manner. Conversely, loss of Nerfin-1 enhances the ability of winner cells to eliminate loser cells in multiple scenarios of cell competition. We further show that INSM1, the mammalian ortholog of Nerfin-1, plays a conserved role in repressing the activity of the TEAD-YAP complex. These findings reveal a novel regulatory mode converging on the transcriptional output of the Hippo pathway that may be exploited for modulating the YAP oncoprotein in cancer and regenerative medicine. KW - Hippo signaling KW - cell competition KW - transcription factors JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -