Related Experiment Video

Updated: Apr 1, 2026

Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases
06:56

Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases

Published on: September 6, 2024

877

Tankyrase Inhibitors Target YAP by Stabilizing Angiomotin Family Proteins

Wenqi Wang1, Nan Li1, Xu Li1

  • 1Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Cell Reports
|October 13, 2015
PubMed

Insights

Tankyrase inhibitors stabilize anigomotin proteins, suppressing the oncoprotein YAP. This discovery reveals a new therapeutic strategy targeting the tankyrase-RNF146-AMOT axis for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Yes-associated protein (YAP) is a key Hippo pathway effector and an oncoprotein with elevated expression in many human cancers.
  • Developing targeted therapies for YAP has been challenging, limiting treatment options.

Purpose of the Study:

  • To investigate the potential of tankyrase inhibitors in suppressing YAP activity.
  • To elucidate the molecular mechanisms underlying YAP regulation by tankyrases and related proteins.

Main Methods:

  • Utilized tankyrase inhibitors to modulate YAP activity in cancer models.
  • Investigated the interaction between tankyrases, anigomotin (AMOT) family proteins, and the E3 ligase RNF146.
  • Assessed the impact of tankyrase inhibition on AMOT protein stability and YAP oncogenic functions.

Main Results:

  • Tankyrase inhibitors were found to suppress YAP activity.
  • This suppression is mediated by the stabilization of anigomotin (AMOT) family proteins.
  • Tankyrases were shown to promote AMOT degradation via RNF146; inhibitors counteract this, stabilizing AMOT and inhibiting YAP.

Conclusions:

  • The tankyrase-RNF146-AMOT axis represents a critical upstream regulator of YAP.
  • Targeting this axis with tankyrase inhibitors offers a promising therapeutic strategy for cancers driven by YAP.
  • This study opens new avenues for developing YAP-targeted cancer therapies.

More Related Videos

Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles10:30

Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles

Published on: October 15, 2014

21.1K

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
4.0K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.9K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
4.3K
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
2.8K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
4.9K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.1K