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 Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>