Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New binding target for oncogenic viral protein

28.02.2005


The DNA tumor virus simian virus 40 produces the Large T antigen which inactivates two of the cell’s most important cancer-preventing proteins, p53 and pRb. In a study published in the Journal of Biological Chemistry, researchers at the Fred Hutchinson Cancer Research Center report the discovery of an additional target for T antigen--a protein called Fbw7.



The Fbw7 gene is located in a chromosomal region that is deleted in up to 30% of human tumors. "Fbw7 is itself an important tumor suppressor which makes it an attractive choice for inactivation by Large T," explained Dr. Markus Welcker, the study’s first author.

The research appears as the "Paper of the Week" in the March 4 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.


DNA tumor viruses proliferate by hijacking their host cell’s DNA replication machinery. In order to do this, they have evolved mechanisms to override normal cellular replication controls. Simian virus 40 (SV40) accomplishes this task by producing the highly oncogenic large T antigen. This protein corrupts the cellular checkpoint mechanisms that guard cell division and the transcription, replication and repair of DNA. T antigen also inactivates some of the most important proteins that protect cells against malignant transformation, including tumor suppressor proteins p53 and pRb.

In the Journal of Biological Chemistry paper, Dr. Welcker and Dr. Bruce Clurman report that T antigen also binds to another tumor suppressor, Fbw7. This protein is part of a ubiquitin ligase complex that adds ubiquitin to proteins to mark them for destruction by the cell. Fbw7 recognizes a destruction signal on certain proteins that need to be degraded and brings them in close proximity to the enzymes that attach ubiquitin. The proteins recognized by Fbw7 play key roles in cell division, cell growth, differentiation, and cell death. "These proteins are also some of the most broadly acting cellular oncogenes, and include cyclin E, c-Myc, Notch, and c-Jun," noted Dr. Clurman. "When Fbw7 is mutated in cancers, deregulation of these oncogenic Fbw7 targets is thought to contribute to cancer. SV40 T antigen contains a motif that mimics the destruction signal found in these proteins." However, unlike the other substrates recognized by Fbw7, T antigen is not destroyed by the cell.

Drs. Clurman and Welcker suspect that by acting as a decoy and binding to Fbw7, T antigen protects cellular Fbw7 targets that facilitate viral replication and tumorigenesis. "I think this work underlines the importance of Fbw7 as an emerging tumor suppressor and the consequences of its loss in tumors," Dr. Welcker emphasized.

"The study of DNA tumors viruses has been an extremely important tool in understanding the cellular pathways that regulate cell division and are disrupted in cancer. Understanding the mechanisms through which these viruses interact with the cellular machinery that regulates cell division may lead to new insights into the pathways that cause cancer. This is an important step to designing new cancer treatment strategies that target these pathways," concluded Dr. Clurman.

Nicole Kresge | EurekAlert!
Further information:
http://www.asbmb.org
http://www.jbc.org

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>