Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A decade later, gene discovered by Temple researchers found to be multi-functional

12.02.2003


A gene discovered by Temple University researchers a decade ago has proved to be multi-functional, with the discovery of its important roles in cell differentiation, HIV transcription, and tumorigenesis.



Cdk9 (cyclin-dependent kinases) and cdk10 were originally isolated by Antonio Giordano, M.D., Ph.D., then a researcher in Temple’s Fels Cancer Institute, and his team in 1992. They are members of a family of kinases originally referred to as a PITALRE, which is the name of the amino acids sequence that is similar to all in this kinase family (http://landesbioscience.com/journals/cancerbio/papersinpress/1.4/cbt03040266.html).

"We were screening a human DNA library in order to look for members of this family and we found cdk9, a gene that encodes for a protein that has the size of 43 kilodaltons," says Giordano, now director of the Sbarro Institute for Cancer Research and Molecular Medicine in Temple’s College of Science and Technology (http://www.temple.edu/news_media/hkg696.html).


Over the next 10 years, cdk9 would prove to be a "multi-functional" gene, playing many different roles.

According to Giordano, among the many functions of cdk9 that have been discovered, one of the most interesting is the role of this kinase in cellular differentiation, particularly muscle differentiation.

"In practical terms, when we overexpress this protein, we are able to promote myogenic differentiation by enhancing the myoD function," says Giordano, who also discovered the tumor suppressing gene Rb2/p130. "Our studies demonstrate that in human tissue, cdk9 is a very important player in specialized tissue, such as muscle or lymphoid tissue."

Another important discovery, says Giordano, shows that if cdk9 is inhibited, or blocked, it prevents the promotion of differentiation, suggesting that this kinase plays a central role in controlling muscle differentiation by regulating directly, genes and their products, such as myoD that is specific for muscle.

"Cdk9 is not only involved in this muscle program, but its specific role in muscle differentiation is important in other programs, such as neurons and astrocytes maturation," he adds. "In addition, cdk9 has been found by several researchers to play a clinical role in other important processes such as apoptosis and in the regulation of the HIV protein Tat."

More recently, based on the discovery of cdk9’s role in muscle differentiation, Giordano collaborated with Dr. Michael D. Schneider of the DeBakey Heart Center at the Baylor University College of Medicine, who demonstrated that cdk9 can be used to block life-threatening hypertrophy or enlargement of the heart. Their study was published in the November 2002 issue of Nature Medicine (www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v8/n11/abs/nm778.html).

An immunologic role for cdk9 has also been discovered and was reported this past fall in Oncogene by Giordano in collaboration with Professor Piero Tosi’s group at the University of Siena in Italy. They have shown that it interacts with gp130, the receptor of the Interleukin-6 (IL-6) family of cytokines.

This discovery, says Dr. Michele Maio, Director of the Cancer Bioimmunotherapy Unit of the Centro di Riferimento Oncologico of Aviano in Italy and adjunct professor at Temple, highlights a totally new biologic role of cdk9. "This should allow us to take advantage of IL-6 as therapeutic agents for targeted therapy in selected histotypes of human cancer."

"Cdk9 acts preferentially by controlling processes such as transcription and the balance between differentiation and apoptosis (programmed cell death), suggesting the important role this kinase can have in controlling or blocking important cellular processes. This is important also from a clinical point of view," concludes Giordano, a cancer specialist who is now actively investigating the role of cdk9 in cancer.

Initial clinical trials of a potent inhibitor of cdk9 function, flavopiridol, are now underway at the National Institutes of Health’s National Cancer Institute (NIH/NCI) in collaboration with Aventis Pharmaceutics. Dr. Adrian M. Senderowicz, Principal Investigator and Chief, Molecular Therapeutics Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, conducted the first clinical trials with this agent at NIH’s Clinical Center.

Based on his encouraging results, several clinical trials worldwide are now being conducted, with a Phase 3 clinical trial in lung cancer being carried out at different research centers in the world, assuring that the multi-functional legacy of cdk9 continues to grow well into the future.

Preston M. Moretz | EurekAlert!
Further information:
http://www.temple.edu/
http://www.temple.edu/news_media/hkg696.html

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>