Navigation Links
A switch that controls whether cells pass point of no return
Date:3/23/2008

DURHAM, N.C. Investigators at the Duke Institute for Genome Sciences and Policy have revealed the hidden properties of an on-off switch that governs cell growth.

The Duke team proved that if the switch is on, then a cell will divide, even if its damaged or the signal to grow disappears. Showing how the switch works may provide clues to novel drug targets for cancer and other diseases in which cell growth goes awry.

The switch is part of a critical pathway that controls cell division, the process by which the body makes new cells. Before a cell starts to divide, it goes through a checklist to make sure everything is in order, much like preparing for a long trip. If a cell senses something is wrong early on, it can halt the process. But once a cell passes a milestone called the restriction point, theres no turning back, no matter the consequences. The switch controls this milestone and is key to cell growth.

The results will appear in the April issue of the journal Nature Cell Biology. The study was funded by the National Institutes of Health, the National Science Foundation and a David and Lucile Packard Fellowship.

The switch is part of the Rb-E2F signaling pathway. Rb, or retinoblastoma, is a key tumor suppressor gene, and E2F is a transcription factor that governs the expression of all the genes important for cells to grow.

The wiring diagram is fundamentally the same. Its very likely that different organisms have evolved a very conserved design principle to regulate their growth, said Guang Yao, Ph.D., lead study author and a postdoctoral fellow in Dukes department of molecular genetics and microbiology.

The cellular pathway that includes the switch is found in all multi-cellular life, from plants to people. A cell decides to trigger the pathway when it receives an external chemical signal to grow.

During the project, the researchers discovered the switch has an unexpected property: it is bistable. Once turned on by an external signal, the switch can maintain its on state, even if the signal disappears.

It was an engineer, Lingchong You, Ph.D., who recognized that the switch might represent a bistable condition. You, an assistant professor of biomedical engineering in Dukes Pratt School of Engineering and an Institute for Genome Sciences & Policy (IGSP) investigator, works next door to Yao and his postdoctoral advisor Joseph Nevins, Ph.D., a professor of molecular genetics at the IGSP.

During conversations with Nevins and Yao about the restriction point phenomenon, You realized that the process could be described as a bistable switch.

The collaboration continued as the scientists broke down the pathway into individual chemical reactions that could be described by mathematical equations. Graduate student Tae Jun Lee worked with Yao to develop and analyze a mathematical model that predicted the switch could be bistable and identified the critical decision maker at the restriction point. Yao verified the results in laboratory experiments on single cells.

Nevins, who has studied the Rb-E2F pathway for 20 years, sees an opportunity to extend this approach to other critical aspects of cell behavior, such as the decisions involved in cell death.

This pathway, and this decision whether it is time to proliferate, is very tightly coupled to decisions of cell fate, Nevins said. Theres a decision as to whether the proliferation process is normal, and if the answer is not, then the result is that the cell dies. We dont know critical dynamics of that process.


'/>"/>

Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

Related biology news :

1. Switching goals
2. Researchers find signal that switches on eye development -- could lead to eye in a dish
3. Researchers identify how to switch off cancer cell genes
4. Leading cause of death in preemies might be controlled by resetting a molecular switch
5. Why the switch stays on
6. Electronic switch opens doors in rheumatoid joints
7. Search for the on switches may reveal genetic role in development and disease
8. Circadian clock controls plant growth hormone
9. Too much sugar turns off gene that controls the effects of sex steroids
10. Technique controls nanoparticle size, makes large numbers
11. Protein controls blood vessel formation, offers new drug target
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/24/2016)... , May 24, 2016 Ampronix facilitates superior patient care by providing unparalleled ... medical LCD display is the latest premium product recently added to the range of ... ... ... Sony 3d Imaging- LCD Medical Display- Ampronix News ...
(Date:5/3/2016)... 2016  Neurotechnology, a provider of high-precision biometric ... Biometric Identification System (ABIS) , a complete system ... ABIS can process multiple complex biometric transactions with ... fingerprint, face or iris biometrics. It leverages the ... MegaMatcher Accelerator , which have been used ...
(Date:4/19/2016)... The new GEZE SecuLogic access ... "all-in-one" system solution for all door components. It can ... door interface with integration authorization management system, and thus ... minimal dimensions of the access control and the optimum ... offer considerable freedom of design with regard to the ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... 27, 2016 , ... Cancer experts from Austria, Hungary, Switzerland, ... a new and helpful biomarker for malignant pleural mesothelioma. Surviving Mesothelioma has just ... now. , Biomarkers are components in the blood, tissue or body fluids ...
(Date:6/27/2016)... June 27, 2016  Liquid Biotech ... funding of a Sponsored Research Agreement with The ... cells (CTCs) from cancer patients.  The funding will ... levels correlate with clinical outcomes in cancer patients ... will then be employed to support the design ...
(Date:6/24/2016)... ... June 24, 2016 , ... While the majority of commercial spectrophotometers and fluorometers ... the 6000i models are higher end machines that use the more unconventional z-dimension of ... beam from the bottom of the cuvette holder. , FireflySci has developed several ...
(Date:6/23/2016)... , June 23, 2016   Boston Biomedical ... novel compounds designed to target cancer stemness pathways, ... been granted Orphan Drug Designation from the U.S. ... of gastric cancer, including gastroesophageal junction (GEJ) cancer. ... designed to inhibit cancer stemness pathways by targeting ...
Breaking Biology Technology: