Related Experiment Videos
Yorkie/YAP Interactors: Fine-Tuning the Hippo Pathway Output
Alexey Veraksa1, Kenneth H Moberg2
1Department of Biology, University of Massachusetts Boston, Boston, Massachusetts 02125, USA alexey.veraksa@umb.edu kmoberg@emory.edu.
Cold Spring Harbor Perspectives in Biology
|August 10, 2026
Summary
The Hippo signaling pathway is fine-tuned by additional regulators, or "tuners," that control the activity of key effectors like Yorkie (Yki)/Yes-associated protein 1 (YAP1). These tuners impact Yki/YAP1 levels and nuclear functions, influencing cellular outcomes.
Area of Science:
- Cell Biology
- Molecular Biology
- Signal Transduction
Background:
- The Hippo signaling pathway is a crucial regulator of organ size and cell proliferation.
- Canonical Hippo pathway components, including MST and LATS kinases, control the nuclear localization and activity of effectors like YAP1/TAZ.
- Emerging evidence indicates additional regulators modulate Hippo pathway activity.
Purpose of the Study:
- To review the diverse "tuners" that fine-tune Hippo pathway activity.
- To highlight the mechanisms by which these tuners regulate YAP1/TAZ.
- To discuss the implications of these regulatory networks for cellular outcomes.
Main Methods:
- Literature review of studies in flies and mammals.
- Analysis of protein-protein interactions, including PPxY motif/WW domain interactions.
- Examination of subcellular localization and degradation pathways.
Main Results:
- Multiple "tuners" associate with YAP1/TAZ at endosomal membranes, the cell cortex, and in the nucleus.
- These tuners regulate YAP1/TAZ turnover, nucleocytoplasmic shuttling, and degradation.
- Nuclear tuners direct specific cellular outcomes through unique transcriptional programs with YAP1/TAZ.
Conclusions:
- Hippo pathway regulation is more complex than previously thought, involving numerous "tuners" that modulate YAP1/TAZ.
- These tuners influence YAP1/TAZ levels and activity through sequestration and degradation.
- Understanding the coordination of these tuners is crucial for deciphering Hippo pathway functions in vivo.