Navigation Links
Researchers discover second protective role for tumor-suppressor

HOUSTON - ATM, a protein that reacts to DNA damage by ordering repairs or the suicide of the defective cell, plays a similar, previously unknown role in response to oxidative damage outside of the nucleus, researchers report this week in the online version of the Proceedings of the National Academy of Sciences.

"This tumor-suppressor that works in the nucleus to prevent replication of defective cells also has a second life out in the cytoplasm, which was totally unexpected," said senior author Cheryl Walker, Ph.D., professor in The University of Texas M. D. Anderson Cancer Center Department of Carcinogenesis.

"ATM recognizes damage caused by reactive oxygen species (ROS) and tells the cell to stop growing by suppressing the protein-synthesizing pathway mTORC1 or orders the cell to consume itself, a process called autophagy," Walker said. This pathway parallels the protein's role of damage recognition and response in the nucleus.

Reactive oxygen species are a byproduct of cellular metabolism and in small amounts play a role in cell signaling. Their ability to react with other molecules makes them toxic, and they are kept in check by antioxidant enzymes. When that natural balance is disrupted, elevated levels of these volatile molecules damage proteins, lipids and DNA, Walker said.

The authors note that elevated ROS has been linked to more than 150 diseases, including diabetes, cancer, neurodegenerative diseases and atherosclerosis.

In its previously known role, ATM (short for Ataxia-Telangiectasia Mutated) senses DNA damage, orders the cell to repair the damage and halts cell division pending repair via the tumor suppressor p53. If repair is not possible, ATM sets off apoptosis - programmed cell death. ATM is commonly mutated in cancer.

The added protective role discovered by the researchers also points to a potential way to activate the tumor-suppressor without damaging DNA.

Walker's lab was studying another tumor-suppressing protein called TSC2 that is active in the cellular cytoplasm and found that ATM appeared to be associated with TSC2 activation.

In a series of experiments, the research team uncovered the molecular pathway that begins with ROS activation of ATM which then:

  • Activates the tumor suppressor LKB1, which in turn phosphorylates and activates the AMP kinase (AMPK), a key player in energy sensing and growth factor signaling.

  • AMPK switches on the tumor-suppressor TSC2 (tuberous sclerosis complex 2).

  • TSC2 then suppresses the kinase mTOR (mammalian Target of Rapamycin), which shuts down the mTORC1 signaling pathway, an important regulator of protein creation and cell growth.

  • Because TORC1 suppresses autophagy, when TORC1 is suppressed by TSC2, autophagy is free to occur.

During autophagy, membranes form around organelles in the cytoplasm, which are subsequently digested. Autophagy plays a normal role in cell growth and stability, and is a natural cellular defense mechanism, providing nutrients for a starving cell, for example.

Autophagy also is thought to be a second form of programmed cell death, because it can eventually kill the cell, cannibalizing it and leaving it shot full of cavities. Whether autophagy is activated as a survival mechanism in response to ROS or as an ATM-driven programmed cell death remains to be explored, the authors noted.

Even so, the study links oxidative stress to a key metabolic pathway activated by ATM that integrates damage response pathways with energy signaling, protein synthesis and cell survival.


Contact: Scott Merville
University of Texas M. D. Anderson Cancer Center

Related medicine news :

1. Stanford researchers find culprit in aging muscles that heal poorly
2. UCLA researchers identify markers that may predict diabetes in still-healthy people
3. Mayo Clinic researchers discover new diagnostic test for detecting infection in prosthetic joints
4. Bipolar disorder relapses halved by Melbourne researchers
5. Cell that triggers symptoms in allergy attacks can also limit damage, Stanford researchers find
6. High and mighty: first common height gene identified by researchers behind obesity gene finding
7. Researchers estimate about 9 percent of US children age 8 to 15 meet criteria for having ADHD
8. Majority of 2.4 Million U.S. Children With ADHD Not Diagnosed or Consistently Treated, According to New Gold Standard Study by Cincinnati Childrens Researchers
9. Researchers develop long-lasting growth hormone
10. Jefferson immunology researchers halt lethal rabies infection in brain
11. Purdue researchers develop technology to detect cancer by scanning surface veins
Post Your Comments:
(Date:6/24/2016)... MIAMI, Fla. (PRWEB) , ... June 24, 2016 , ... ... Florida Trend magazine’s 2016 Legal Elite. The attorneys chosen by their peers for this ... of Florida. , Seven Greenberg Traurig Shareholders received special honors as members of this ...
(Date:6/24/2016)... ... June 24, 2016 , ... Comfort Keepers® of San Diego, CA is excited ... To Recovery® program to drive cancer patients to and from their cancer treatments. ... highest quality of life and ongoing independence. Getting to and from medical treatments ...
(Date:6/24/2016)... Plano, TX (PRWEB) , ... June 24, 2016 , ... ... taking part in Genome magazine’s Code Talker Award, an essay contest in which patients ... for an award to be presented at the 2016 National Society of Genetic Counselors ...
(Date:6/24/2016)... York, NY (PRWEB) , ... June 24, 2016 ... ... publication Haute Living, is proud to recognize Dr. Barry M. Weintraub as a ... that “the most beautiful women in the world, and the most handsome men, ...
(Date:6/24/2016)... , ... June 24, 2016 , ... ... actively feeding the Frederick area economy by obtaining investment capital for emerging technology ... past 2½ years that have already resulted in more than a million dollars ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... announced the establishment of Astellas Farma Colombia (AFC), a new affiliate with operations headquartered in Bogota. Colombia ... ... ... ... Astellas is a pharmaceutical ...
(Date:6/23/2016)... , June 23, 2016 The vast majority ... outpatient dialysis facility.  Treatments are usually 3 times a ... per visit, including travel time, equipment preparation and wait ... but especially grueling for patients who are elderly and ... skilled nursing and rehabilitation centers for some duration of ...
(Date:6/23/2016)... YORK , June 23, 2016 ... waters, but it continues to present great opportunities to ... companies for today: Intrexon Corp. (NYSE: XON ... Arena Pharmaceuticals Inc. (NASDAQ: ARNA ), and ... more about these stocks and receive your complimentary trade ...
Breaking Medicine Technology: