Related Experiment Video

Updated: Jun 14, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

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

A non-canonical repressor function of JUN restrains YAP activity and liver cancer growth

Yuliya Kurlishchuk1, Anita Cindric Vranesic1, Marco Jessen1

  • 1Transcriptional Control of Tissue Homeostasis Lab, Leibniz Institute on Aging, Fritz Lipmann Institute e.V., Beutenbergstr. 11, 07745, Jena, Germany.

The EMBO Journal
|August 29, 2024
PubMed

Insights

JUN, a component of AP-1, acts as a specific repressor of YAP/TAZ activity. A negative feedback loop involving JUN and YAP/TAZ is disrupted in liver cancer, promoting tumor growth.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Gene regulation

Background:

  • The Hippo pathway regulates organ size by controlling the activity of transcriptional coactivators Yes-associated protein (YAP) and its homolog, transcriptional coactivator with PDZ-binding motif (TAZ).
  • Uncontrolled YAP/TAZ activity is linked to excessive cell growth and tumor formation, highlighting the importance of regulatory mechanisms.

Purpose of the Study:

  • To investigate the regulatory mechanisms controlling YAP/TAZ activity.
  • To identify novel repressors of YAP/TAZ function.
  • To elucidate the role of AP-1 components in YAP/TAZ regulation.

Main Methods:

  • Investigated the interaction between AP-1 components and YAP/TAZ.
  • Assessed the impact of JUN on YAP/TAZ transcriptional activity at shared target sites.
  • Examined the JUN-dependent negative feedback loop in normal and cancerous liver cells.

Main Results:

  • Identified JUN, an AP-1 component, as a specific repressor of YAP/TAZ activity at joint target sites.
  • Demonstrated that JUN's repressive function is independent of its canonical AP-1 heterodimerization with FOS.
  • Discovered a negative feedback loop where YAP/TAZ induces JUN expression, which in turn suppresses YAP/TAZ activity.
  • Found this feedback loop disrupted in liver cancer, leading to unrestrained YAP/TAZ oncogenic potential.

Conclusions:

  • JUN acts as a critical repressor of YAP/TAZ, independent of canonical AP-1 functions.
  • A novel JUN-dependent negative feedback loop buffers YAP/TAZ activity.
  • Disruption of this feedback loop in liver cancer contributes to oncogenesis by unleashing YAP/TAZ's full potential.
Keywords:
AP-1HippoJUNLiver CancerYAP

More Related Videos

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs10:32

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs

Published on: December 19, 2019

10.8K
In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines08:50

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines

Published on: April 18, 2025

365

Related Concept Videos

Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.3K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.7K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.2K
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
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.0K