Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Global signaling study suggests cancer link to protein promiscuity

17.11.2005


Haphazard activation of secondary signaling pathways may fuel cancer’s genesis



When found at abnormally high concentrations, two proteins implicated in many human cancers have the potential to spur indiscriminate biochemical signaling inside cells, chemists at Harvard University have found. Their finding may expand scientists’ current understanding of oncogenesis -- that cancer arises when an oncoprotein becomes overactive, ramping up the biochemical pathways that it normally activates -- suggesting that an important additional mechanism could be the inappropriate activation of numerous secondary pathways.

"Our data offer a new way to think about cancer, adding to the current paradigm," says Gavin MacBeath, an assistant professor of chemistry and chemical biology in Harvard’s Faculty of Arts and Sciences and co-author of a paper published in the journal Nature. "We present the hypothesis that an important component of oncogenesis is the ability of proteins to turn on alternative, secondary signaling pathways when overexpressed, rather than simply upregulating primary pathways."


MacBeath and colleagues studied the four human ErbB receptors, which set in motion widely studied cellular processes including cell migration, adhesion, growth and death. These receptors span the cell membrane; the external portion binds free growth factors, creating biochemical signals propagated inside the cell.

Each ErbB receptor has multiple intracellular binding sites where proteins can dock, but MacBeath’s group found that only two of the four ErbB proteins, known as EGFR and ErbB2, become dramatically more "promiscuous" -- able to recruit and activate a large number of different signaling proteins -- when present at high concentrations.

"These two promiscuous ErbB proteins are known to be overactive in many human cancers, suggesting that their ability to turn on rampant signaling may contribute to their high oncogenic potential," MacBeath says. "This newfound link may also offer alternative strategies for therapeutic intervention. Many of today’s cancer pharmaceuticals work by targeting individual receptors such as EGFR and ErbB2. Our work suggests that new drugs could target critical secondary pathways that are inappropriately activated by promiscuous proteins."

The researchers studied interactions between signaling proteins and the ErbB receptors using a protein microarray technique developed by MacBeath in 2000, when he was a research fellow in Harvard’s Bauer Center for Genomic Research. This method can rapidly and simultaneously assess the strength of interactions among tens of thousands of proteins genome-wide. The current research analyzed the interactions between 159 proteins and 33 binding sites on the four ErbB receptors. The scientists looked not only at whether a given protein-receptor pair interacted, but also how strongly.

Steve Bradt | EurekAlert!
Further information:
http://www.harvard.edu

More articles from Studies and Analyses:

nachricht The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig

nachricht Win-win strategies for climate and food security
02.10.2017 | International Institute for Applied Systems Analysis (IIASA)

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>