Forum für Wissenschaft, Industrie und Wirtschaft

Hauptsponsoren:     3M 
Datenbankrecherche:

 

Protein balance key in preventing cancer

28.02.2013
Fox Chase researchers find that two antagonistic proteins help keep leukemia at bay, pointing to new potential treatments

Two proteins that scientists once thought carried out the same functions are actually antagonists of each other, and keeping them in balance is key to preventing diseases such as cancer, according to new findings published in the February 25 issue of Developmental Cell by scientists at Fox Chase Cancer Center. The results suggest that new compounds could fight cancer by targeting the pathways responsible for maintaining the proper balance between the proteins.

"It's our job now to understand how we can intervene therapeutically in this system, so we can restore balance when it's thrown off," says study author David L. Wiest, PhD, professor and deputy chief scientific officer at Fox Chase.

The two proteins—"Rpl22" and "Rpl22-like1", which contribute to the process by which additional cellular proteins are made—are created from two similar genes, leading researchers to previously believe they were performing identical functions in the body. "What we're finding is that is absolutely not true," says Wiest. "Not only are they performing different functions, they are antagonizing each other."

During the study, Wiest and his team knocked out Rpl22 in zebrafish—a common model of human disease. Without Rpl22, the zebrafish don't develop a type of T cells (a blood cell) that helps fight infections. The same developmental defect was observed when they knocked out Rpl22-like1, indicating that both proteins are independently required to enable stem cells to give rise to T cells.

But when the researchers tried to restore T cells in zebrafish that lacked Rpl22 by adding back Rpl22-like1, it didn't work. The reverse was also true—Rpl22 was not enough to restore function after the researchers eliminated Rpl22-like1. These results led Wiest and his team to believe that, although the proteins are both involved in producing stem cells, they do not perform the same function.

To learn more about the proteins' individual functions, the researchers looked at the levels of different proteins involved in stem cell production when either Rpl22 or Rpl22-like1 was absent. Without Rpl22-like1, cells had lower levels of a protein known as Smad1—a critical driver of stem cell development. And when Rpl22 disappeared, levels of Smad1 increased dramatically.

Both proteins can bind directly to the cellular RNA from which Smad1 is produced, suggesting that they maintain balance in stem cell production via their antagonistic effects on Smad1 expression, explains Wiest.

"I like to think of Rpl22 as a brake, and Rpl22-like1 as a gas pedal – in order to drive stem cell production, both have to be employed properly. If one or the other is too high, this upsets the balance of forces that regulate stem cell production, with potentially deadly effects," says Wiest.

Specifically, too much Rpl22 (the "brake"), and stem cell production shuts off, decreasing the number of blood cells and leading to problems such as anemia. Too much Rpl22-like1 (the "gas pedal"), on the other hand, can create an over-production of stem cells, leading to leukemia.

Previous research has found that Rpl22-like1 is often elevated in cancer, including 80% of cases of acute myeloid leukemia (AML). Conversely, researchers have found that in other cancers, the gene that encodes Rpl22 is deleted. "Either one of these events is sufficient to alter the balance in stem cell production in a way that pushes towards cancer," says Wiest.

Co-authors on the study include Yong Zhang, Anne-Cécile E. Duc, Shuyun Rao, Xiao-Li Sun, Alison N. Bilbee, Michele Rhodes, Qin Li, Dietmar J. Kappes, and Jennifer Rhodes of Fox Chase.

Fox Chase Cancer Center, part of Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation's first cancer hospitals, Fox Chase also was among the first institutions to receive the National Cancer Institute's prestigious comprehensive cancer center designation in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are routinely recognized in national rankings, and the Center's nursing program has achieved Magnet status for excellence three consecutive times. Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research and oversees programs in cancer prevention, detection, survivorship, and community outreach. For more information, call 1-888-FOX-CHASE (1-888-369-2427) or visit www.foxchase.org.

Diana Quattrone | EurekAlert!
Further information:
http://www.fccc.edu

Further reports about: Nobel Prize Protein Rpl22-like1 T cells blood cell cellular protein stem cells

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Entwicklung miniaturisierter Lichtmikroskope - „ChipScope“ will ins Innere lebender Zellen blicken

Das Institut für Halbleitertechnik und das Institut für Physikalische und Theoretische Chemie, beide Mitglieder des Laboratory for Emerging Nanometrology (LENA), der Technischen Universität Braunschweig, sind Partner des kürzlich gestarteten EU-Forschungsprojektes ChipScope. Ziel ist es, ein neues, extrem kleines Lichtmikroskop zu entwickeln. Damit soll das Innere lebender Zellen in Echtzeit beobachtet werden können. Sieben Institute in fünf europäischen Ländern beteiligen sich über die nächsten vier Jahre an diesem technologisch anspruchsvollen Projekt.

Die zukünftigen Einsatzmöglichkeiten des neu zu entwickelnden und nur wenige Millimeter großen Mikroskops sind äußerst vielfältig. Die Projektpartner haben...

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Das anwachsende Ende der Ordnung

Physiker aus Konstanz weisen sogenannte Mermin-Wagner-Fluktuationen experimentell nach

Ein Kristall besteht aus perfekt angeordneten Teilchen, aus einer lückenlos symmetrischen Atomstruktur – dies besagt die klassische Definition aus der Physik....

Im Focus: Wegweisende Erkenntnisse für die Biomedizin: NAD⁺ hilft bei Reparatur geschädigter Erbinformationen

Eine internationale Forschergruppe mit dem Bayreuther Biochemiker Prof. Dr. Clemens Steegborn präsentiert in 'Science' neue, für die Biomedizin wegweisende Forschungsergebnisse zur Rolle des Moleküls NAD⁺ bei der Korrektur von Schäden am Erbgut.

Die Zellen von Menschen und Tieren können Schäden an der DNA, dem Träger der Erbinformation, bis zu einem gewissen Umfang selbst reparieren. Diese Fähigkeit...

Im Focus: Designer-Proteine falten DNA

Florian Praetorius und Prof. Hendrik Dietz von der Technischen Universität München (TUM) haben eine neue Methode entwickelt, mit deren Hilfe sie definierte Hybrid-Strukturen aus DNA und Proteinen aufbauen können. Die Methode eröffnet Möglichkeiten für die zellbiologische Grundlagenforschung und für die Anwendung in Medizin und Biotechnologie.

Desoxyribonukleinsäure – besser bekannt unter der englischen Abkürzung DNA – ist die Trägerin unserer Erbinformation. Für Prof. Hendrik Dietz und Florian...

Alle Focus-News des Innovations-reports >>>

Anzeige

Anzeige

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

Industriearbeitskreis »Prozesskontrolle in der Lasermaterialbearbeitung ICPC« lädt nach Aachen ein

28.03.2017 | Veranstaltungen

Neue Methoden für zuverlässige Mikroelektronik: Internationale Experten treffen sich in Halle

28.03.2017 | Veranstaltungen

Wie Menschen wachsen

27.03.2017 | Veranstaltungen

 
VideoLinks
B2B-VideoLinks
Weitere VideoLinks >>>
Aktuelle Beiträge

Von Agenten, Algorithmen und unbeliebten Wochentagen

28.03.2017 | Unternehmensmeldung

Hannover Messe: Elektrische Maschinen in neuen Dimensionen

28.03.2017 | HANNOVER MESSE

Dimethylfumarat – eine neue Behandlungsoption für Lymphome

28.03.2017 | Medizin Gesundheit