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 Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>