Hergovich Alexander
Tumour Suppressor Signalling Networks Laboratory, UCL Cancer Institute, University College London, London, UK.
EMBO Rep. 2017 Jan;18(1):3-4. doi: 10.15252/embr.201643622. Epub 2016 Dec 15.
The Hippo growth control pathway coordinates cell proliferation, death, differentiation and stemness through regulatory phosphorylation of the YAP proto‐oncoprotein, a major nuclear effector of Hippo signalling. In particular, YAP phosphorylation on Ser127 can promote inhibitory 14‐3‐3 interactions and cytoplasmic sequestration. Two studies in this issue of show that Ser128 phosphorylation of YAP by the Nemo‐like kinase (NLK) disrupts 14‐3‐3 interactions, thereby promoting nuclear accumulation of active YAP 1, 2. Notably, Ser127‐phosphorylated YAP can be nuclear and co‐transcriptionally active upon osmotic stress, thus, challenging the dogma of YAP regulation by Ser127 phosphorylation.
河马生长控制通路通过对YAP原癌蛋白进行调节性磷酸化来协调细胞增殖、死亡、分化和干性,YAP是河马信号传导的主要核效应因子。特别是,YAP第127位丝氨酸的磷酸化可促进抑制性14-3-3相互作用和细胞质隔离。本期的两项研究表明,Nemo样激酶(NLK)使YAP的第128位丝氨酸磷酸化,破坏了14-3-3相互作用,从而促进了活性YAP的核积累。值得注意的是,在渗透压应激下,第127位丝氨酸磷酸化的YAP可以进入细胞核并具有共转录活性,因此,挑战了通过第127位丝氨酸磷酸化来调节YAP的传统观念。