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Updated: Apr 15, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
Histidine phosphorylation of NME1 regulates the Hippo pathway via the ARHGAP17-CDC42-cytoskeleton axis
Xian Liu1, Zhongnan Chen1, Jianxi Zhu1
1MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Guangzhou Key Laboratory of Healthy Aging Research, School of Life Sciences, Institute of Healthy Aging Research, Sun Yat-sen University, Guangzhou 510275, China.
Abstract:
NME1 is a key metastasis suppressor whose activity depends on histidine phosphorylation, yet the biological significance of this modification remains poorly understood. Here, we reveal a previously unrecognized role for NME1 in regulating the Hippo pathway. Using PhastID-based proximity labeling combined with functional assays, we demonstrate that NME1 modulates CDC42 activity via ARHGAP17, a GTPase-activating protein, thereby influencing cytoskeletal organization and Hippo activation. Loss of NME1 reduced YAP phosphorylation and promoted its nuclear localization, indicating suppression of Hippo signaling. These findings define a histidine phosphorylation-dependent NME1-ARHGAP17-CDC42-cytoskeleton axis that controls the Hippo pathway, providing new insights into the functional repertoire of NME1 in cancer and development.
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