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Updated: Feb 21, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
USP21 regulates Hippo pathway activity by mediating MARK protein turnover
Hung Thanh Nguyen1, Jan-Michael Kugler1, Anand C Loya2
1Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
The Hippo pathway regulates cancer growth via YAP/TAZ activity. USP21 deubiquitylase controls this by affecting MARK kinases, suggesting USP21 as a potential biomarker for renal clear cell carcinoma.
Area of Science:
- Molecular Biology
- Cancer Biology
- Biochemistry
Background:
- The Hippo pathway, involving YAP/TAZ transcriptional co-activators, acts as a tumor suppressor.
- While YAP/TAZ are rarely mutated in cancer, their elevated activity is linked to poor prognosis.
- Ubiquitin-mediated protein degradation regulates Hippo pathway components, and its dysregulation is implicated in cancer.
Purpose of the Study:
- To identify novel regulators of the Hippo pathway.
- To investigate the role of USP21 in controlling YAP/TAZ activity and its implications in cancer.
Main Methods:
- Investigated the role of USP21 in regulating Hippo pathway signaling.
- Assessed the impact of USP21 on the stability of MARK kinases.
- Analyzed USP21 expression in renal clear cell carcinoma samples.
Main Results:
- USP21 was identified as a novel regulator of the Hippo pathway.
- USP21 controls YAP/TAZ activity by modulating the stability of MARK kinases.
- Low USP21 expression was observed in early-stage renal clear cell carcinoma.
Conclusions:
- USP21 plays a critical role in regulating Hippo pathway activity through MARK kinase stability.
- USP21 represents a potential biomarker for early-stage renal clear cell carcinoma.
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