Related Experiment Video

Updated: Jun 30, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

19.8K

The tumor suppressor NF2 modulates TEAD4 stability and activity in Hippo signaling via direct interaction

Mengying Wu1, Liqiao Hu1, Lingli He2

  • 1Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

The Journal of Biological Chemistry
|March 24, 2024
PubMed

Insights

The tumor suppressor NF2 directly binds and inhibits TEAD4, a key transcription factor in the Hippo pathway. This interaction destabilizes TEAD4, suppressing cell proliferation and revealing a new tumor suppression mechanism.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • The Hippo signaling pathway regulates organ size by controlling cell proliferation.
  • Yeast Transcriptional Enhancer Activator protein (YAP) and TEAD transcription factors are key downstream effectors of the Hippo pathway.
  • The tumor suppressor NF2 is known to interact with the Hippo pathway, but its direct role in regulating TEAD has been unclear.

Purpose of the Study:

  • To investigate whether NF2 directly interacts with and regulates TEAD transcription factors.
  • To elucidate the mechanism by which NF2 might influence TEAD activity.
  • To determine if the interaction between NF2 and TEAD is essential for NF2's tumor suppressive functions.

Main Methods:

  • Co-immunoprecipitation assays to detect physical interaction between NF2 and TEAD4.
  • Western blotting to assess protein stability and ubiquitination.
  • Immunofluorescence microscopy to track subcellular localization of TEAD4.
  • Cell proliferation assays to evaluate the functional significance of the NF2-TEAD4 interaction.

Main Results:

  • A direct physical interaction between NF2 and TEAD4 was identified.
  • NF2 binding decreased TEAD4 protein stability and inhibited its palmitoylation, independent of LATS1/2 and YAP.
  • NF2 induced TEAD4 cytoplasmic translocation, leading to ubiquitination and dysfunction.
  • The interaction between NF2 and TEAD4 was crucial for NF2's ability to suppress cell proliferation.

Conclusions:

  • NF2 directly binds to TEAD4, acting as an inhibitor.
  • NF2 suppresses TEAD4 activity through destabilization, altered localization, and ubiquitination, independent of canonical Hippo pathway kinases.
  • This interaction represents a novel mechanism for NF2 tumor suppressor activity within the Hippo signaling cascade.
Keywords:
Hippo pathwayNF2TEAD4palmitoylationprotein‒protein interactiontumor suppressor

More Related Videos

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

6.9K
Culturing and Manipulation of O9-1 Neural Crest Cells08:32

Culturing and Manipulation of O9-1 Neural Crest Cells

Published on: October 9, 2018

10.1K

Related Concept Videos

Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.4K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.5K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K