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

ABSTRACT: 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.

SUBMITTER: Lim S

PROVIDER: S-EPMC6449379 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Lim Sanghee S Hermance Nicole N Mudianto Tenny T Mustaly Hatim M HM Mauricio Ian Paolo Morelos IPM Vittoria Marc A MA Quinton Ryan J RJ Howell Brian W BW Cornils Hauke H Manning Amity L AL Ganem Neil J NJ

Nature communications 20190404 1

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 cellula ...[more]

PMID: 30948712

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Dataset Information

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

Publications

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

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