커뮤니티

Global Group

Best your Partner

연구소세미나

게시글 검색
Identification of the kinase STK25 as an upstream activator of LATS signaling.
종양연구소 조회수:255
2019-05-17 12:54:04

Identification of the kinase STK25 as an upstream activator of LATS signaling.

 

2019 Apr 4;10(1):1547. doi: 10.1038/s41467-019-09597-w.

 

The Hippo pathway maintains tissue homeostasis by negatively regulating the oncogenic transcriptional co-activators YAP and TAZ. Though functional inactivation of the Hippo pathway is common in tumors, mutations in core pathway components are rare. Thus, understanding how tumor cells inactivate Hippo signaling remains a key unresolved question. Here, we identify the kinase STK25 as an activator of Hippo signaling. We demonstrate that loss of STK25 promotes YAP/TAZ activation and enhanced cellular proliferation, even under normally growth-suppressive conditions both in vitro and in vivo. Notably, STK25 activates LATS by promoting LATS activation loop phosphorylation independent of a preceding phosphorylation event at the hydrophobic motif, which represents a form of Hippo activation distinct from other kinase activators of LATS. STK25 is significantly focally deleted across a wide spectrum of human cancers, suggesting STK25 loss may represent a common mechanism by which tumor cells functionally impair the Hippo tumor suppressor pathway.

SNS 공유