Research & Development World

  • Home Page
  • Topics
    • Aerospace
    • Archeology
    • Automotive
    • Biotech
    • Chemistry
    • COVID-19
    • Environment
    • Energy
    • Life Science
    • Material Science
    • R&D Market Pulse
    • R&D Management
    • Physics
  • Technology
    • 3D Printing
    • A.I./Robotics
    • Battery Technology
    • Controlled Environments
      • Cleanrooms
      • Graphene
      • Lasers
      • Regulations/Standards
      • Sensors
    • Imaging
    • Nanotechnology
    • Scientific Computing
      • Big Data
      • HPC/Supercomputing
      • Informatics
      • Security
      • Software
    • Semiconductors
  • 2021 R&D 100 Award Winners
    • R&D 100 Awards
    • 2020 Winners
    • Winner Archive
  • Resources
    • Digital Issues
    • Podcasts
    • Subscribe
  • Global Funding Forecast
  • Webinars

USP15 Shows Promise As Therapeutic Target

By R&D Editors | February 21, 2012

After years studying the molecular bases of glioblastoma – the most common brain tumor and one of the most aggressive of all cancers, the group led by Dr. Joan Seoane, Director of Translational Research at the Vall d’Hebron Institute of Oncology (VHIO) and ICREA Research Professor, has published a study in Nature Medicine identifying USP15 as a critical protein in cancer which, thanks to its molecular characteristics, shows enormous therapeutic promise.

USP15 promotes tumor progression by activating the TGF? pathway. Playing a highly significant oncogenic role in glioblastoma, TGFß is a powerful immunosuppressant allowing the tumor to escape the host immune system. It also acts as an angiogenic factor inducing blood vessels, promotes tumoral invasion, activates cancer stem cells, and in some tumors, induces metastases.

Dr. Seoane’s team has unmasked the USP15 enzyme as activator of the TGF? chain reaction. In tumors the USP15-TGFß axis is deregulated due to USP15 gene amplification leading to an aberrant TGFß activation.

USP15 acts by controlling and correcting the TGF? activity in the same way that a thermostat regulates temperature. If the TGF? activity is high, it reduces; and if it is low, it increases the TGF? activity. USP15 therefore achieves optimal TGF? activity.

Protein stability is regulated through the elimination or aggregation of ubiquitins, small proteins that establish which molecules need to be eliminated. This process is finely regulated by deubiquitinating enzymes (DUBs) such as USP15 which determine the correct level of a protein under certain physiological conditions. In this orchestrated manner, USP15 controls and adapts the TGF? receptor stability and, therefore, the activity of the pathway.

The problem arises when, in some tumors, the USP15 gene is amplified due to genetic mutations and the enzyme is over produced. The thermostat breaks down and is therefore only sensing the “cold” resulting in the overactivation of the TGF? pathway. Remarkably, this is not only a phenomenum of glioblastomas since the USP15 gene has also been found activated in other types of cancer such as breast or ovarian cancer.

Dr. Joan Seoane explained “When we inhibited USP15 in a real model of human glioblastoma, TGF? activity decreased and the tumor did not develop. USP15 regulates tumor progression and is critical in cancer.”

Sometimes potentially powerful therapeutic targets are found but are not pharmacologically accessible due to their biochemical characteristics. “Enzymes in general – particularly deubiquitinating enzymes (DUBs) such as USP15, can easily be deactivated and are therefore good therapeutic targets”, Seoane commented, “our results, generated thanks to the funding received from the Spanish Association Against Cancer (AECC), show exciting new promise in improved treatment of cancer patients.”

Date: February 19, 2012
Source: Vall d´Hebron Institute of Oncology 

Related Articles Read More >

New dangers in the woods — and the hope that research offers us
Novel mass spectrometry solution simplifies insight gathering into macromolecular complexes
ENPICOM launches display solution to accelerate antibody selection while maximizing precision
Thermo Fisher Scientific autoimmune-testing instruments now available in the U.S.
2021 R&D Global Funding Forecast

Need R&D World news in a minute?

We Deliver!
R&D World Enewsletters get you caught up on all the mission critical news you need in research and development. Sign up today.
Enews Signup

R&D World Digital Issues

February 2020 issue

Browse the most current issue of R&D World and back issues in an easy to use high quality format. Clip, share and download with the leading R& magazine today.

Research & Development World
  • Subscribe to R&D World Magazine
  • Enews Sign Up
  • Contact Us
  • About Us
  • Drug Discovery & Development
  • Pharmaceutical Processing
  • 2022 Global Funding Forecast

Copyright © 2022 WTWH Media LLC. All Rights Reserved. The material on this site may not be reproduced, distributed, transmitted, cached or otherwise used, except with the prior written permission of WTWH Media
Privacy Policy | Advertising | About Us

Search R&D World

  • Home Page
  • Topics
    • Aerospace
    • Archeology
    • Automotive
    • Biotech
    • Chemistry
    • COVID-19
    • Environment
    • Energy
    • Life Science
    • Material Science
    • R&D Market Pulse
    • R&D Management
    • Physics
  • Technology
    • 3D Printing
    • A.I./Robotics
    • Battery Technology
    • Controlled Environments
      • Cleanrooms
      • Graphene
      • Lasers
      • Regulations/Standards
      • Sensors
    • Imaging
    • Nanotechnology
    • Scientific Computing
      • Big Data
      • HPC/Supercomputing
      • Informatics
      • Security
      • Software
    • Semiconductors
  • 2021 R&D 100 Award Winners
    • R&D 100 Awards
    • 2020 Winners
    • Winner Archive
  • Resources
    • Digital Issues
    • Podcasts
    • Subscribe
  • Global Funding Forecast
  • Webinars