We recently reported the identification of a novel component of the Hippo pathway: Mask. The Mask protein contains multiple ankyrin repeats which bind to the Yki/YAP transcriptional activator.
In addition Mask features a KH domain that can bind to nucleic acids. The protein also contains nuclear import and export sequences and appears to be regulated in a highly similar fashion to Yki/YAP proteins. Mask is also essential for Yki/YAP proteins to induce target gene transcription to normal levels.
We have been able to co-purify a complex of Mask, Yki and Scalloped (a Yki-binding transcription factor) by pulling down a promoter DNA sequence from a Yki target gene. Thus, we propose that Mask acts in the nucleus to promote Yki-mediated transcription.
The discovery of Mask provides a new entry point to investigate how Yki/YAP proteins are physiologically regulated in vivo. To date, the only known mechanism of Yki/YAP regulation has been phosphorylation by the Warts/LATS kinase. However, Mask does not appear to be regulated by Warts/LATS activity, which suggests that other signals must be important for regulating both Yki/YAP and Mask in different contexts.
Since Yki/YAP proteins are often nuclear in human epithelial stem cells and cancers and can strongly drive cell proliferation, understanding precisely how the activity of these proteins is regulated is a key goal in understanding cancer.