# Role of DHX29 in the regulation of Hippo pathway effectors YAP/TAZ in cancer

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2020 · $33,283

## Abstract

Project Summary Abstract
 The Hippo signaling pathway is a well-conserved pathway that controls tissue homeostasis and organ
size. Activation of an upstream phosphorylation cascade through this pathway leads to the suppression of the
transcriptional co-activators YAP/YAP1 and TAZ/WWTR1. Because these two proteins regulate the transcription
of genes involved in cell proliferation, apoptosis, and stem cell self-renewal, precise control of their activity and
abundance is imperative for normal development and organismal homeostasis. Indeed, altered expression or
inactivation of Hippo pathway genes has been observed in many human cancer patient samples and has been
shown to drive tumorigenesis in mouse models. Despite the established importance of Hippo signaling in cancer,
there still remains a lack of complete characterization of Hippo pathway regulation as few mutations in the
pathway are found in human cancers, suggesting the role of other upstream inputs and signaling cross talk.
 The goal of this proposal is to identify and characterize novel regulators of the Hippo pathway effectors
YAP/TAZ to gain a more comprehensive understanding of the Hippo signaling network as it pertains to normal
cellular physiology and cancer progression. To gain insight into the regulation of YAP/TAZ, I have performed a
gene-trap mutagenesis screen in a haploid cell line expressing a TAZ-fluorescent fusion protein. Unexpectedly,
a number of RNA-binding proteins were identified from the screen. Because one gene candidate DHX29, an
RNA helicase reported to promote translation and play a role in cell proliferation, had the most robust phenotype
upon validation and correlated strongly with YAP/TAZ levels across a panel of cancer cell lines, this proposal
will seek to characterize the role of translational regulation on YAP/TAZ activity and its impact on YAP/TAZ-
mediated tumorigenesis. Aim 1 will determine the functional role of DHX29 on the regulation of YAP/TAZ activity.
Aim 2 will characterize its role in YAP/TAZ-mediated tumorigenesis.
 Successful completion of the proposed research will elucidate a novel regulatory mechanism of the Hippo
pathway effectors in the context of tumor development. As activation of YAP/TAZ in different tissues in mouse
models suggests the role of the Hippo pathway in cancer initiation and progression, characterizing a novel
regulatory network will inform mechanisms of cancer pathogenesis and identify potential therapeutic handles for
modulating tumor progression.

## Key facts

- **NIH application ID:** 9833436
- **Project number:** 5F31CA235893-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Priscilla Cheung
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $33,283
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9833436

## Citation

> US National Institutes of Health, RePORTER application 9833436, Role of DHX29 in the regulation of Hippo pathway effectors YAP/TAZ in cancer (5F31CA235893-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9833436. Licensed CC0.

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