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

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 |
Cathy Yarbrough
U.S. communications representative
for Singapore A*STAR
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

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

Adela Foo | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Enormous dome in central Andes driven by huge magma body beneath it

25.10.2016 | Earth Sciences

First time-lapse footage of cell activity during limb regeneration

25.10.2016 | Life Sciences

Deep down fracking wells, microbial communities thrive

25.10.2016 | Earth Sciences

More VideoLinks >>>