Related Experiment Video

Updated: Apr 5, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.9K

Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis

Lin Yuan1,2, Yanrong Lv3, Hongchang Li1

  • 1State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.

Nature Cell Biology
|August 18, 2015
PubMed

Insights

Researchers identified OTUD3 as a deubiquitylase that stabilizes PTEN, a key tumor suppressor. Loss of OTUD3 promotes cancer progression and metastasis, highlighting the OTUD3-PTEN axis in tumor suppression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • PTEN is a critical tumor suppressor frequently altered in cancer.
  • While PTEN's ubiquitin ligases are known, its stabilizing deubiquitylase remains largely uncharacterized.
  • Reduced PTEN protein stability contributes to tumorigenesis.

Purpose of the Study:

  • To identify and characterize the deubiquitylase responsible for PTEN stabilization.
  • To elucidate the role of this deubiquitylase in cancer development and progression.

Main Methods:

  • Biochemical assays to confirm OTUD3's deubiquitylase activity on PTEN.
  • In vitro and in vivo experiments assessing PTEN stability and Akt signaling.
  • Analysis of OTUD3 expression and mutations in human cancer samples.
  • Generation and analysis of OTUD3 transgenic mice.

Main Results:

  • OTUD3 was identified as a deubiquitylase that directly interacts with and de-polyubiquitylates PTEN, enhancing its stability.
  • OTUD3 depletion resulted in PTEN degradation, Akt pathway activation, cellular transformation, and metastasis.
  • OTUD3 transgenic mice showed increased PTEN levels and resistance to tumorigenesis.
  • Reduced OTUD3 expression and loss-of-function mutations in OTUD3 were correlated with human breast cancer progression.

Conclusions:

  • OTUD3 is a crucial deubiquitylase that stabilizes PTEN, acting as a tumor suppressor.
  • The OTUD3-PTEN signaling pathway is vital for maintaining tumor suppression.
  • Dysregulation or mutation of OTUD3 contributes to human cancer development and progression.

More Related Videos

Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples09:45

Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples

Published on: May 10, 2015

10.2K
In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

11.6K

Related Concept Videos

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...
5.4K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
9.9K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
9.3K
Regulated Protein Degradation02:58

Regulated Protein Degradation

3.4K
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...
6.3K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

2.1K