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 Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>