Epithelial Biology Laboratory, Francis Crick Institute, London, United Kingdom.
EMBL Australia, ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
Elife. 2019 Oct 29;8:e48601. doi: 10.7554/eLife.48601.
Mask family proteins were discovered in 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.
在果蝇中发现了膜相关蛋白家族，以促进转录共激活因子 Yorkie（Yki）的活性，Yki 是哺乳动物 YAP（YAP1）和 TAZ（WWTR1）的唯一同源物。膜相关蛋白家族的分子功能，或者其哺乳动物同源物 Mask1（ANKHD1）和 Mask2（ANKRD17），仍然不清楚。膜相关蛋白家族包含两个锚蛋白重复结构域，可与 Yki/YAP 结合，以及一个保守的核定位序列（NLS）和核输出序列（NES），这表明它们在核质转运中起作用。在这里，我们表明 Mask 可促进 Yki 的核内输入，并且向 Yki 添加异位 NLS 足以绕过 Mask 在 Yki 驱动的组织生长中的作用。哺乳动物的 Mask1/2 蛋白也可促进 YAP 的核内输入，并稳定 YAP 并驱动液滴的形成。Mask1/2 和 YAP 通常在细胞核和细胞质中以颗粒状方式共定位，并且在机械转导过程中受到共同调节。
