Forum für Wissenschaft, Industrie und Wirtschaft

Hauptsponsoren:     3M 
Datenbankrecherche:

 

New mechanism for cancer progression discovered by UNC and Harvard researchers

27.11.2012
The protein Ras plays an important role in cellular growth control. Researchers have focused on the protein because mutations in its gene are found in more than 30 percent of all cancers, making it the most prevalent human oncogene.
University of North Carolina Lineberger Comprehensive Cancer Center and Harvard researchers have discovered an alternative mechanism for activating Ras that does not require mutation or hormonal stimulus. In healthy cells, Ras transmits hormone signals into the cell that prompt responses such as cell growth and the development of organs and tissues. A mutation on the RAS gene can chronically activate those signals, leading to tumor initiation and progression.

In an article published on-line in a November issue of Nature Structural and Molecular Biology, the UNC and Harvard teams discovered that modification of Ras at a specific site with a small protein known as ubiquitin can also lock Ras into an active signaling state. Thus, modification of Ras with a single ubiquitin – a process known as monoubiquitination - switches Ras to an active signaling state by disrupting the action of another protein known as the GTPase activating protein, or GAP. Work by two of the papers co-authors, Atsuo Sasaki and Lewis Cantley of Harvard, had previously found evidence for Ras’s potential to become activated and promote Ras-mediated tumorigenesis by monoubiquitination.

Because of the strong link between Ras and cancer, Ras should be an attractive target for drug discovery efforts. Despite considerable efforts at developing treatments targeting the protein, Ras itself is now considered to be ‘undruggable’, leading researchers to try new approaches to developing drugs that target activated Ras. This could lead to benefits beyond cancer therapies, as the RAS gene has also been linked to developmental disorders such as Noonan syndrome, Costello syndrome and autoimmune lymphoproliferative syndrome.

Lead researcher Rachael Baker, a PhD candidate doing joint work in the labs of Henrik Dohlman, PhD, professor of pharmacology and vice chair of biochemistry and biophysics and Sharon Campbell, PhD, professor of biochemistry and biophysics at UNC, developed a novel method to modify Ras with ubiquitin and then subsequently characterized how ubiquitin modification can lead to Ras activation.

The attachment of ubiquitin to Ras at a specific site leads to Ras activation, much like with an oncogenic mutation, leading to an increased potential for cancer formation. Baker notes that the reaction can be reversed by enzymes in the cell that remove ubiquitin, making these enzymes possible targets for future pharmaceutical research.

“Establishing how Ras is activated by ubiquitin is just the first step in understanding this novel mechanism of cellular regulation.” said Campbell.

The researchers next step will be to obtain a more detailed understanding of its role in cancer progression, first in cells and in animals and eventually in cancer patients.

Research was done in conjunction with Brian Kuhlman and Steven Lewis in the UNC Department of Biochemistry and Biophysics. The work was supported by NIH grants R01CA089614 (S.L.C.), R01GM073180–06S1 (H.G.D.), R01GM073960 and R01GM073151, and R01GM41890 and P01CA117969 (L.C.C.), the Program in Molecular and Cellular Biophysics and NIH grant T32GM008570, the Japanese Society for the Promotion of Science Research Fellowship for Research Abroad, Kanae Foundation for Research Abroad and a Genentech Fellowship.

William Davis | EurekAlert!
Further information:
http://www.unc.edu

More articles from Life Sciences:

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Reibungswärme treibt hydrothermale Aktivität auf Enceladus an

Computersimulation zeigt, wie der Eismond Wasser in einem porösen Gesteinskern aufheizt

Wärme aus der Reibung von Gestein, ausgelöst durch starke Gezeitenkräfte, könnte der „Motor“ für die hydrothermale Aktivität auf dem Saturnmond Enceladus sein....

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: Kleine Strukturen – große Wirkung

Innovative Schutzschicht für geringen Verbrauch künftiger Rolls-Royce Flugtriebwerke entwickelt

Gemeinsam mit Rolls-Royce Deutschland hat das Fraunhofer-Institut für Werkstoff- und Strahltechnik IWS im Rahmen von zwei Vorhaben aus dem...

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: Transparente Beschichtung für Alltagsanwendungen

Sport- und Outdoorbekleidung, die Wasser und Schmutz abweist, oder Windschutzscheiben, an denen kein Wasser kondensiert – viele alltägliche Produkte können von stark wasserabweisenden Beschichtungen profitieren. Am Karlsruher Institut für Technologie (KIT) haben Forscher um Dr. Bastian E. Rapp einen Werkstoff für solche Beschichtungen entwickelt, der sowohl transparent als auch abriebfest ist: „Fluoropor“, einen fluorierten Polymerschaum mit durchgehender Nano-/Mikrostruktur. Sie stellen ihn in Nature Scientific Reports vor. (DOI: 10.1038/s41598-017-15287-8)

In der Natur ist das Phänomen vor allem bei Lotuspflanzen bekannt: Wassertropfen perlen von der Blattoberfläche einfach ab. Diesen Lotuseffekt ahmen...

Alle Focus-News des Innovations-reports >>>

Anzeige

Anzeige

IHR
JOB & KARRIERE
SERVICE
im innovations-report
in Kooperation mit academics
Veranstaltungen

Kinderanästhesie aktuell: Symposium für Ärzte und Pflegekräfte

23.11.2017 | Veranstaltungen

IfBB bei 12th European Bioplastics Conference mit dabei: neue Marktzahlen, neue Forschungsthemen

22.11.2017 | Veranstaltungen

Zahnimplantate: Forschungsergebnisse und ihre Konsequenzen – 31. Kongress der DGI

22.11.2017 | Veranstaltungen

 
VideoLinks
B2B-VideoLinks
Weitere VideoLinks >>>
Aktuelle Beiträge

Kinderanästhesie aktuell: Symposium für Ärzte und Pflegekräfte

23.11.2017 | Veranstaltungsnachrichten

Seminar „Leichtbau im Automobil- und Maschinenbau“ im Haus der Technik Berlin am 16. - 17. Januar 2018

23.11.2017 | Seminare Workshops

Biohausbau-Unternehmen Baufritz erhält von „ Capital“ die Auszeichnung „Beste Ausbilder Deutschlands“

23.11.2017 | Unternehmensmeldung