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 New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>