Angiomotin'g YAP into the nucleus for cell proliferation and cancer development.

The Hippo pathway regulates cell proliferation and apoptosis during development, tissue regeneration, and carcinogenesis. Nuclear translocation of the transcription factors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) and their subsequent interaction with TEA domain (TEAD) transcriptional factors program pro-proliferative and antiapoptotic transcription. Scaffold proteins angiomotin (Amot) and angiomotin-related AmotL1 and AmotL2 were recently identified as negative regulators of YAP and TAZ by preventing their nuclear translocation. In this issue of Science Signaling, Yi et al. show that Amot may also promote nuclear translocation of YAP and act as a transcriptional cofactor of the YAP-TEAD complex to facilitate proliferation of biliary epithelial cells and cancer development of the liver either in response to tissue injury or in the absence of the tumor suppressor Merlin. These seemingly controversial results highlight that our understanding of Amot proteins in the Hippo pathway is so far limited.