Featured Research

from universities, journals, and other organizations

Neurons, brain cancer cells require the same little-known protein for long-term survival

Date:
July 15, 2014
Source:
University of North Carolina School of Medicine
Summary:
Researchers show how the protein PARC/CUL9 helps neurons and brain cancer cells override the biochemical mechanisms that lead to cell death in most other cells.

In brain cancer cells, the protein PARC plays a key role in long-term cell survival. In both images, the red represents the protein cytochrome c, which is released when mitochondria are damaged and trigger apoptosis -- cell suicide. At left, injured brain cancer cells exhibit little cytochrome c; they use the protein PARC to degrade the released cytochrome c, allowing the cancer cells to survive. At right, when researchers reduced PARC, cytochrome c accumulated, allowing apoptosis to carry on.
Credit: Vivian Gama, PhD, UNC School of Medicine

Researchers at the UNC School of Medicine have discovered that the protein PARC/CUL9 helps neurons and brain cancer cells override the biochemical mechanisms that lead to cell death in most other cells. In neurons, long-term survival allows for proper brain function as we age. In brain cancer cells, though, long-term survival contributes to tumor growth and the spread of the disease.

These results, published in the journal Science Signaling, not only identify a previously unknown mechanism used by neurons for their much-needed survival, but show that brain cancer cells hijack the same mechanism for their own survival.

The discovery will lead to new investigations of brain cancer treatments and provides insight into Parkinson's disease, including a potential new research tool for scientists.

"PARC is very similar to Parkin, a protein that's mutated in Parkinson's disease," said Mohanish Deshmukh, a professor of cell biology and physiology and senior author of the Science Signaling paper. "We think they might work in tandem to protect neurons."

If so, researchers can investigate the interplay between these proteins to create better drugs to treat the second-most prevalent neurodegenerative disease after Alzheimer's disease.

Vivian Gama, PhD, a postdoctoral fellow in Deshmukh's lab, led the experiments in cell cultures and animal models. First, she used external stimuli to promote the damage of mitochondria -- the energy sources for cells. In most cell types, when mitochondria are damaged, they release a protein called cytochrome c, which triggers a cascade of biochemical steps that end in cell death -- a process known as apoptosis.

Working with neurons, though, Gama found that the protein PARC/CUL9 blocked this process; it degraded cytochrome c, halted apoptosis, and allowed for long-term cell survival. "In this setting, we want PARC to do that because we want neurons to survive as long as possible," said Gama, first author of the Science Signaling paper.

Deshmukh, a member of the UNC Neuroscience Center and the UNC Lineberger Comprehensive Cancer Center, said, "In Parkinson's disease, we know that Parkin targets damaged mitochondria for degradation. However, exactly what happens to the proteins, such as cytochrome c, that are released from the damaged mitochondria has been unknown. Now, we think PARC plays a role in this process."

Deshmukh and Gama's work could lead to an alternative way to study Parkinson's disease. Other researchers have created mouse models that lack the Parkin gene, but Gama said these models don't have many of the hallmark symptoms that human patients have, making the model less than desirable for researchers. "Our hypothesis is that in the absence of Parkin, PARC still does the job," Gama said, "as it may allow cells to survive."

Gama and Deshmukh are now creating a model that lacks both the Parkin and PARC genes.

They will also investigate PARC as a target for cancer treatment.

"We tested several cancer cell lines and found that PARC degrades cytochrome c in medulloblastoma, a cancer of the central nervous system and in neuroblastoma, a cancer of the peripheral nervous system," Gama said. "Not all cytochrome c is degraded; there are likely other factors involved. But PARC is an important player."

When Gama and colleagues triggered the apoptotic process in brain cancer cells, they found that PARC allowed the cells to survive. When PARC was inhibited, the cells were more vulnerable to stress and damage, which means they could be more vulnerable to compounds aimed at destroying them.

Deshmukh said, "We show that brain cancer cells co-opt PARC to bypass apoptosis in the same way that neurons do and for the exact same purpose."


Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. V. Gama, V. Swahari, J. Schafer, A. J. Kole, A. Evans, Y. Huang, A. Cliffe, B. Golitz, N. Sciaky, X.-H. Pei, Y. Xiong, M. Deshmukh. The E3 ligase PARC mediates the degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells. Science Signaling, 2014; 7 (334): ra67 DOI: 10.1126/scisignal.2005309

Cite This Page:

University of North Carolina School of Medicine. "Neurons, brain cancer cells require the same little-known protein for long-term survival." ScienceDaily. ScienceDaily, 15 July 2014. <www.sciencedaily.com/releases/2014/07/140715141345.htm>.
University of North Carolina School of Medicine. (2014, July 15). Neurons, brain cancer cells require the same little-known protein for long-term survival. ScienceDaily. Retrieved September 30, 2014 from www.sciencedaily.com/releases/2014/07/140715141345.htm
University of North Carolina School of Medicine. "Neurons, brain cancer cells require the same little-known protein for long-term survival." ScienceDaily. www.sciencedaily.com/releases/2014/07/140715141345.htm (accessed September 30, 2014).

Share This



More Health & Medicine News

Tuesday, September 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How 'Yes Means Yes' Defines Sexual Assault

How 'Yes Means Yes' Defines Sexual Assault

Newsy (Sep. 29, 2014) Aimed at reducing sexual assaults on college campuses, California has adopted a new law changing the standard of consent for sexual activity. Video provided by Newsy
Powered by NewsLook.com
Scientists May Have Found An Early Sign Of Pancreatic Cancer

Scientists May Have Found An Early Sign Of Pancreatic Cancer

Newsy (Sep. 29, 2014) Researchers looked at 1,500 blood samples and determined people who developed pancreatic cancer had more branched chain amino acids. Video provided by Newsy
Powered by NewsLook.com
Colo. Doctors See Cluster of Enterovirus Cases

Colo. Doctors See Cluster of Enterovirus Cases

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com
Dr.'s Unsure of Cause of Fast-Spreading Virus

Dr.'s Unsure of Cause of Fast-Spreading Virus

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins