PT  - JOURNAL ARTICLE
AU  - Clara Sidor
AU  - Nerea Borreguero-Munoz
AU  - Georgina C Fletcher
AU  - Ahmed Elbediwy
AU  - Hannah Vanyai
AU  - Oriane Guillermin
AU  - Barry J Thompson
TI  - Mask family proteins ANKHD1 and ANKRD17 regulate YAP nuclear import, stability and phase separation
AID  - 10.1101/595439
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 595439
4099  - http://biorxiv.org/content/early/2019/04/01/595439.short
4100  - http://biorxiv.org/content/early/2019/04/01/595439.full
AB  - The Mask family of multiple ankyrin repeat and KH domain proteins were discovered in Drosophila to promote the activity of the transcriptional coactivator Yorkie (Yki), the sole fly homolog of mammalian YAP (YAP1) and TAZ (WWTR1). The molecular function of Mask, or its mammalian homologs Mask1 (ANKHD1) and Mask2 (ANKRD17), remains unclear. Mask family proteins contain two Ankyrin repeat domains that bind Yki/YAP as well as a conserved nuclear localisation sequence (NLS) and nuclear export sequence (NES), suggesting a role in nucleo-cytoplasmic transport. Here we show that Mask acts to promote nuclear import of Yki, and that addition of an ectopic NLS to Yki is sufficient to bypass the requirement for Mask in Yki-driven tissue growth. Mammalian Mask1/2 proteins also promote nuclear import of YAP, as well as stabilising YAP and driving colloidal phase separation into large liquid droplets. Mask1/2 and YAP normally colocalise in a granular fashion in both nucleus and cytoplasm, and are co-regulated during mechanotransduction. Our results suggest that Mask family proteins promote YAP nuclear import and phase separation to regulate YAP stability and transcriptional activity.