Related Experiment Video

Updated: Feb 10, 2026

siRNA Screening to Identify Ubiquitin and Ubiquitin-like System Regulators of Biological Pathways in Cultured Mammalian Cells
10:43

siRNA Screening to Identify Ubiquitin and Ubiquitin-like System Regulators of Biological Pathways in Cultured Mammalian Cells

Published on: May 24, 2014

11.8K

PTPN12/PTP-PEST Regulates Phosphorylation-Dependent Ubiquitination and Stability of Focal Adhesion Substrates in

Zhihua Chen1, John E Morales1, Paola A Guerrero1

  • 1Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas.

Cancer Research
|May 11, 2018
PubMed

Insights

A novel mechanism involving PTP-PEST protein regulates glioblastoma (GBM) invasion by controlling the stability of key focal adhesion proteins, impacting cancer cell growth and spread.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Glioblastoma (GBM) is an aggressive brain cancer characterized by invasive tumor cells that lead to recurrent disease.
  • Current treatments are limited by the ability of GBM cells to disperse and evade surgical removal.

Purpose of the Study:

  • To elucidate the regulatory mechanism controlling GBM cell invasion.
  • To identify key proteins involved in GBM cell motility and stability.

Main Methods:

  • Investigated the role of protein tyrosine phosphatase PTP-PEST in GBM.
  • Utilized biochemical assays to study interactions between PTP-PEST, Crk-associated substrate (Cas), and valosin-containing protein (Vcp).
  • Assessed the impact of PTP-PEST modulation on GBM cell invasion in vitro and in vivo mouse models.

Main Results:

  • PTP-PEST physically bridges Cas and Vcp, an ATP-dependent protein segregase.
  • PTP-PEST regulates the phosphorylation of Vcp at tyrosine 805 (Y805), affecting its interaction with Cas and protein stability.
  • Altered PTP-PEST activity modified GBM cell invasion and growth in vitro and in preclinical models.

Conclusions:

  • PTP-PEST plays a critical role in balancing GBM cell growth and invasion.
  • A novel regulatory pathway involving PTP-PEST, Vcp, and Cas controls phosphorylation-dependent ubiquitination of focal adhesion proteins.
  • This mechanism offers potential therapeutic targets for inhibiting GBM cell invasion.

More Related Videos

Using Cell-substrate Impedance and Live Cell Imaging to Measure Real-time Changes in Cellular Adhesion and De-adhesion Induced by Matrix Modification09:11

Using Cell-substrate Impedance and Live Cell Imaging to Measure Real-time Changes in Cellular Adhesion and De-adhesion Induced by Matrix Modification

Published on: February 19, 2015

11.4K
Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

3.2K

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.6K
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
54.3K
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...
8.9K
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....
9.7K
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
26.5K
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
136.5K