Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New findings implicate cell size controls in a variety of diseases

26.11.2003


Basic research into a tumor suppressor gene that controls cell size has uncovered a link between three different genetic diseases and points to a possible treatment for all of them.



The tie that binds these three seemingly disparate medical conditions is a biochemical chain of events that govern cell size. At the end of this chain, a known drug may work to replace missing or broken parts of the biochemical chain.

"We were doing basic cell biology, investigating how cell growth is coordinated with the cell’s energy level," said Kun-Liang Guan, research professor at the University of Michigan Life Sciences Institute. "We found this story that connects all these things together in a logical manner."


Guan, who is also a professor of biological chemistry and a MacArthur Foundation fellow, and postdoctoral fellow Ken Inoki have been investigating the general question of how cell growth is regulated because it can be a factor in cancerous cell growth.

In a study published in the Nov. 26 edition of Cell, the researchers describe how a cell growth regulator gene called TSC2 responds to different levels of available energy, such as the sugar glucose. As expected, they found that TSC2 activity is stepped up in response to energy starvation, which means the cell’s growth rate is being slowed to accommodate the less favorable growing conditions.

TSC1 and TSC2 take their name from a kind of tumor. Tuberous sclerosis is a genetic disease in which benign tumors may grow in the brain and nervous system throughout a person’s life. Its severity can range from learning disabilities and epilepsy to severe mental retardation and uncontrollable seizures. There is no cure for tuberous sclerosis, but symptoms may be treated with medications to control seizures and behavior problems.

The genes TSC1 and TSC2 make two proteins that bind together to form a complex which helps control a cell’s growth and its final size. A defect in either gene can lead to tuberous sclerosis.

In watching how the cell responded to energy shortages, the Guan lab identified a molecule called AMPK that makes TSC2 work harder in starvation conditions.

Though it wasn’t known previously that AMPK was performing this function, the molecule had earlier been implicated in Wolf-Parkinson-White Syndrome, a genetic disease marked by problems in the electrical circuitry of the heart muscle and cardiac hypertrophy, an abnormally enlarged heart.

Upstream in the biochemical reaction from AMPK is another molecule known as LKB1, which was identified by other researchers. Defects in LKB1 are associated with Peutz-Jagers Syndrome, in which benign polyps proliferate in the intestines and stomach, and dark pigmentation appears around the mouth, eyes and nostrils of children under 5.

Guan earlier established that the TSC complex’s job is to limit the activity of a molecule called mTOR, which is a key player in cell growth, protein-making and viability. Now, it’s clear that these other molecules act upstream of mTOR, and that a defect in each of them means a different disease.

Taken together, the chain of events is now known to work like this:
More LKB1 means more AMPK. That means more TSC2, and that, in turn, means less mTOR, which has the result of limiting cell growth. Knock out any of those elements upstream from mTOR, and you have the opposite effect---more cell growth.

This is where Guan scoots forward in his chair excitedly. He recently learned that researchers at the Cincinnati Children’s Hospital are experimenting with the drug Rapamycin to regulate mTOR activity. He has to wonder: what if Rapamycin, which has FDA approval for use as an anti-rejection drug in organ transplants, could also be used to treat these genetic syndromes?

That is, if somebody has a genetic disorder because their AMPK or LKB is missing or malformed, could the role of regulating mTOR be replaced by the drug?

That’s the next question Guan and his team will turn to, working with their Life Sciences Institute colleagues. Guan wants to collaborate with LSI geneticist David Ginsburg on developing mice that mimic the genetic disorders so that further study can be done on the biochemical chain of events. And Guan wants to connect with LSI cell biologist Daniel Klionsky to look for parallels between this mammalian version of TOR (mTOR), and a molecule Klionsky studies in yeast called just TOR which performs similar functions.

"It will be great to have Dan as my neighbor," said Guan, whose office is just steps away from Klionsky’s on the sixth floor of the new LSI. "This is the sort of thing this institute is all about."


The paper is "TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival," Ken Inoki, Tianqing Zhu and Kun-Liang Guan, Cell, Vol. 115, Nov. 26, 2003.

Karl Leif Bates | EurekAlert!
Further information:
http://www.lsi.umich.edu
http://www.lifesciences.umich.edu/institute/labs/guan/
http://www.umich.edu/news

More articles from Health and Medicine:

nachricht On track to heal leukaemia
18.01.2017 | Universitätsspital Bern

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

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...

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

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>