Mask family proteins ANKHD1 and ANKRD17 regulate YAP nuclear import and stability

Sidor, Clara, Borreguero-Munoz, Nerea, Fletcher, Georgina C, Elbediwy, Ahmed, Guillermin, Oriane and Thompson, Barry J (2019) Mask family proteins ANKHD1 and ANKRD17 regulate YAP nuclear import and stability. eLIFE, 2019(8), e48601. ISSN (online) 2050-084X

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Abstract

Mask family 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 formation of liquid droplets. Mask1/2 and YAP normally colocalise in a granular fashion in both nucleus and cytoplasm, and are co-regulated during mechanotransduction.

Item Type: Article
Additional Information: This work was supported by the Wellcome Trust, Cancer Research UK and Medical Research Council [reference number FC001180].
Research Area: Biological sciences
Cancer studies
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing
Faculty of Science, Engineering and Computing > School of Life Sciences, Pharmacy and Chemistry
Depositing User: Ahmed Elbediwy
Date Deposited: 06 Nov 2019 14:13
Last Modified: 13 Feb 2020 13:47
DOI: https://doi.org/10.7554/eLife.48601
URI: http://eprints.kingston.ac.uk/id/eprint/44322

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