Navigation Links
Researchers discover second protective role for tumor-suppressor
Date:2/18/2010

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
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:8/31/2020)... NEW YORK (PRWEB) , ... August 31, 2020 ... ... the nation’s largest non-profit organization devoted exclusively to funding innovative lymphoma research and ... and patient services – today announced the 10th Anniversary of Blood Cancer Awareness ...
(Date:8/31/2020)... ... 2020 , ... Colorado State University Global (CSU Global) – ... education – is proud to announce its new master’s degree in Military ... in the nation, the 60-credit hour program is designed to provide students with ...
(Date:8/31/2020)... Calif. (PRWEB) , ... August 31, 2020 , ... ... leadership experience working, both directly with persons with autism and other developmental disabilities, ... expertise includes early intervention, parent education, adolescents with autism, school consultation, and staff ...
(Date:8/28/2020)... , ... August 28, 2020 , ... ... one-year subscription to a customized Lighthouse Health & Wellness mobile app and web-portal. ... this project. Motorola Solutions Foundation awards grants each year to organizations, such as ...
(Date:8/27/2020)... N.Y. (PRWEB) , ... August 27, 2020 , ... ... DePinto, has joined the Walk-in Dermatology team in its Greenvale, New York location. ... Island Nail and Skin Care Institute. She is certified in chemical peels, microdermabrasion, ...
Breaking Medicine News(10 mins):
(Date:8/26/2020)... ... August 26, 2020 , ... ... into definitive agreement to acquire ProCE, a nationally recognized provider of continuing ... , CEA represents a growing alliance of CME/CE and service organizations ...
(Date:8/26/2020)... (PRWEB) , ... August 26, 2020 , ... ... RN, CHPN, CHPCA, LNC has added CHC and CPCO to her name. , ... Certification in Healthcare Compliance (CHC) and the Certified Professional Compliance Officer (CPCO.) , ...
(Date:8/26/2020)... ... August 26, 2020 , ... The Lymphoma Research Foundation ... research and serving the lymphoma community through education programs, outreach initiatives and patient ... Gala and Charity Auction on Wednesday, Sept. 30 . The “Finding Cures ...
Breaking Medicine Technology: