Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Singapore scientists discover widely sought molecular key to understanding p53 tumor suppressor gene

14.10.2009
How p53 'turns on' genes now better understood

Scientists at the Singapore Immunology Network (SIgN) have determined how the master gene regulator p53 could switch a gene in a cell "on" or "off" by recognizing specific sequences of nucleotides in the gene's DNA.

Their findings provide a missing piece about p53 gene repression that has eluded researchers investigating the master regulator, which undergoes mutations or deletions in over 50 percent of all cancers.

"The precise interaction of p53 with its response elements has been studied for some 20 years, and while we have a good understanding of how p53 turns on genes, no clear answer as to the equally important question of how p53 turns off or 'represses' genes has emerged," said Sir David Lane, Ph.D., a co-discoverer of p53 and now Chief Scientist at Singapore's A*STAR (Agency for Science, Technology and Research), which oversees SIgN.

"The SIgN group's identification of a bona fide 'repressive' response element has provided the missing piece which has eluded p53 researchers for a long time, as well as a definitive key with which to perform future studies," Dr. Lane added.

The findings, highlighted in the Oct. issue of Nature Reviews Cancer and published in the Proceedings of the National Academy of Sciences in August, may allow scientists to confirm the many genes involved in the complex pathways of p53 and, potentially, to uncover new p53 pathways.

The findings also clarify scientists' understanding about the cellular pathways damaged by p53 mutations and may point to areas in the pathways where new cancer targets might be discovered.

The specific sequences of nucleotides, known as response elements, that are recognized by p53 have been very difficult to decipher because they could total over one million possible combinations. In fact, predicting whether p53 actually switched a gene "on" or "off" had been an elusive goal until this recent discovery.

"The findings are truly intriguing," added Dr. Lane, who attributed the SIgN group's success to a combination of sound thinking and the right opportunities. "I expect their findings to have very positive and significant impact on the progress of biomedical research and to help define this vital tumor-fighting pathway."

By applying a systematic approach to analyzing known p53 response elements, the Singapore scientists succeeded in identifying a simpler two-nucleotide core sequence that was sufficient to provide an accurate prediction.

Interestingly, the discovery was made by a SIgN research group, led by Ren Ee Chee, Ph.D., that focuses on immunology rather than molecular biology or genetics.

"We had been studying a metastasis gene which is upregulated in liver cancer called Lasp-15," said Dr. Ren. "As it happened to be under the control of p53, we wanted to determine in detail the role of p53. However we quickly realized that the existing literature was not helpful enough as there were ambiguities over how p53 exerts control over specific genes."

This led to the SIgN researchers' identification of the definitive two-nucleotide sequence, and subsequent establishment of a general set of rules to predict the roles of nucleotides within a response element, which enabled them to correct those of 20 response elements (out of 162 assessed).

Dr. Ren added, "Our findings illustrate how exciting science can be, when innovative discoveries can arise from unexpected sources. They are also proof that frequently in nature, what may seem very complicated at first eventually turns out to be simple and elegant."

Praising the group's efforts, SIgN Scientific Director Paola Castagnoli, Ph.D., said, "This study has significant and far-reaching implications. It will allow for the confirmation of many genes involved in the complex pathways of p53 and, potentially, uncover new p53 pathways. It also clarifies our understanding of which cellular pathways are damaged by p53 mutations and points to areas where new cancer targets might be discovered. I am proud of the group's achievements thus far, and look forward to more exciting findings from them."

The Nature Reviews Cancer article is titled, "Transcription: Reaching a consensus." The SIgN scientists PNAS paper is titled, "Redefining the p53 response element."

For queries and clarification, please contact:
Adela Foo
Senior Officer, Corporate Communications
Agency for Science, Technology and Research (A*STAR)
DID: (+65) 6826 6218 |
Email: adela_foo@a-star.edu.sg
Cathy Yarbrough
U.S. communications representative
for Singapore A*STAR
858-243-1814
sciencematter@yahoo.com
Singapore Immunology Network (SIgN):
SIgN, officially inaugurated in Jan. 2008, is a research consortium under A*STAR's Biomedical Research Council. It is aimed at building on the strengths of the existing immunology research groups at A*STAR, as well as expanding and strengthening the immunology research expertise in Singapore. SIgN's objectives include coordinating basic, translational and clinical research needed to establish immunology as a core capability in Singapore. The major focus areas of research at SIgN are infection and inflammation, in which SIgN researchers investigate immune responses and regulation in disease-specific contexts. Through this, SIgN aims to build up a strong platform in basic human immunology research for better translation of research findings into clinical applications. SIgN also sets out to establish productive links with local initiatives within Biopolis and across Singapore, as well as to obtain international recognition as a leading immunology research hub while establishing relationships with the best institutions in the world. For more information about SIgN, please visit www.sign.a-star.edu.sg

Agency for Science, Technology and Research (A*STAR):

The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences, and physical sciences and engineering research institutes, and seven consortia & centre, which are located in Biopolis and Fusionopolis, as well as their immediate vicinity. A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, hospitals, research centres, and with other local and international partners. For more information about A*STAR, please visit www.a-star.edu.sg

Adela Foo | EurekAlert!
Further information:
http://www.a-star.edu.sg

More articles from Life Sciences:

nachricht Research team creates new possibilities for medicine and materials sciences
22.01.2018 | Humboldt-Universität zu Berlin

nachricht Saarland University bioinformaticians compute gene sequences inherited from each parent
22.01.2018 | Universität des Saarlandes

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Thanks for the memory: NIST takes a deep look at memristors

22.01.2018 | Materials Sciences

Radioactivity from oil and gas wastewater persists in Pennsylvania stream sediments

22.01.2018 | Earth Sciences

Saarland University bioinformaticians compute gene sequences inherited from each parent

22.01.2018 | Life Sciences

VideoLinks Wissenschaft & Forschung
Overview of more VideoLinks >>>