Endosomal phosphatidylserine is critical for the YAP signalling pathway in proliferating cells

Tatsuyuki Matsudaira, Kojiro Mukai, Taishin Noguchi, Junya Hasegawa, Tomohisa Hatta, Shun Ichiro Iemura, Tohru Natsume, Norio Miyamura, Hiroshi Nishina, Jun Nakayama, Kentaro Semba, Takuya Tomita, Shigeo Murata, Hiroyuki Arai*, Tomohiko Taguchi

*この研究の対応する著者

研究成果: Article査読

14 被引用数 (Scopus)

抄録

Yes-associated protein (YAP) is a recently discovered growth-promoting transcription coactivator that has been shown to regulate the malignancy of various cancers. How YAP is regulated is not fully understood. Here, we show that one of the factors regulating YAP is phosphatidylserine (PS) in recycling endosomes (REs). We use proximity biotinylation to find proteins proximal to PS. Among these proteins are YAP and multiple proteins related to YAP signalling. Knockdown of ATP8A1 (an RE PS-flippase) or evectin-2 (an RE-resident protein) and masking of PS in the cytoplasmic leaflet of membranes, all suppress nuclear localization of YAP and YAP-dependent transcription. ATP8A1 knockdown increases the phosphorylated (activated) form of Lats1 that phosphorylates and inactivates YAP, whereas evectin-2 knockdown reduces the ubiquitination and increased the level of Lats1. The proliferation of YAP-dependent metastatic cancer cells is suppressed by knockdown of ATP8A1 or evectin-2. These results suggest a link between a membrane phospholipid and cell proliferation.

本文言語English
論文番号1246
ジャーナルNature communications
8
1
DOI
出版ステータスPublished - 2017 12 1

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

フィンガープリント

「Endosomal phosphatidylserine is critical for the YAP signalling pathway in proliferating cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル