An unexpected player in a cancer defense system

November 28, 2011 in Cancer

Researchers of the Swedish medical university Karolinska Institutet and the University of Cologne, Germany, have identified a new protein involved in a defense mechanism against cancer. The VCP/p97 complex is best known for its role in protein destruction and is involved in a type of familial dementia and ALS. In a novel study the researchers now describe how this complex also plays an important role in regulating the recruitment of the tumor suppressor protein 53BP1 to damaged DNA – suggesting an important role for VCP/p97 in our body's defense against cancer.

Damage of is potentially very dangerous and linked to the development of . Since DNA damage is unavoidable, our cells are equipped with a sophisticated defense system that activates repair mechanisms. This process is initiated by binding of sensor proteins to the damaged DNA that in turn bind and activate other proteins responsible for repairing the damage. During the last decade, it has become clear how many of those proteins are recruited to the damaged DNA, but the mechanism by which the 53BP1 finds its way has been puzzling.

The surprising finding of this study, presented in the scientific journal Nature Structural & Molecular Biology, is not only the identity of the new player but also how it is doing the job. By following proteins in cells with DNA damage, the researchers found that the VCP/p97 complex is among the proteins that are being recruited to DNA damage. This was unanticipated since VCP/p97 is known to be primarily involved in the destruction of defective proteins. VCP/p97 is doing this by unwinding them so that the waste proteins can be chopped in pieces by dedicated enzymes. This important function also explains its involvement in a type of familial and ALS since this kind of waste proteins typically pile up in these diseases.

It turns out that VCP/p97 is doing something similar at damaged DNA although with a very different outcome. The work shows that VCP/p97 facilitates the binding of 53BP1 by removing a that occupies the places where 53BP1 can bind. So instead of unwinding a protein to prepare it for destruction, VCP/p97 pulls a protein out of the way for 53BP1. The researchers also show that worms that have less of this complex are very sensitive to DNA damage supporting an important and evolutionary conserved role of VCP/p97 in DNA damage control. This new mechanism of recruiting a protein by removing another one that gets in the way sheds new light onto how the tumor suppressor 53BP1 finds damaged DNA. An important question that remains is if VCP/p97 plays similar roles in other processes.

More information: 'The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks', Klara Acs, S. Martijn Luijsterburg, Leena Ackermann, Florian A. Salomons, Thorsten Hoppe & Nico P. Dantuma, Nature Structural & Molecular Biology, online November 27 201, DOI: 10.1038/10.1038/nsmb.2188

Journal reference: Nature Structural & Molecular Biology search and more info website

Provided by Karolinska Institutet search and more info website

5 /5 (1 vote)  

Rank 5 /5 (1 vote)
Related Stories
Relevant PhysicsForums posts

More news stories

Molecular marker from pancreatic 'juices' helps identify pancreatic cancer

Researchers at Mayo Clinic have developed a promising method to distinguish between pancreatic cancer and chronic pancreatitis—two disorders that are difficult to tell apart. A molecular marker obtained from pancreatic ...

Cancer created 10 minutes ago | popularity not rated yet | comments 0

New smartphone application improves colonoscopy preparation

The use of a smartphone application significantly improves patients' preparation for a colonoscopy, according to new research presented today at Digestive Disease Week (DDW). The preparation process, which begins days in ...

Cancer created May 19, 2013 | popularity not rated yet | comments 0

Research examines new methods for managing digestive health

Research presented at Digestive Disease Week (DDW) explores new methods for managing digestive health through diet and lifestyle.

Cancer created May 19, 2013 | popularity not rated yet | comments 1

New colonoscope provides ground-breaking view of colon

A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...

Cancer created May 18, 2013 | popularity 5 / 5 (2) | comments 0

ASCO: combo antibody therapy effective for melanoma

(HealthDay)—Concurrent use of two immune checkpoint antibodies—ipilimumab and nivolumab—may be effective for the treatment of advanced melanoma, according to a proof-of-principal study presented in ...

Cancer created May 17, 2013 | popularity not rated yet | comments 0


Blame your parents for bunion woes

A novel study reports that white men and women of European descent inherit common foot disorders, such as bunions (hallux valgus) and lesser toe deformities, including hammer or claw toe. Findings from the Framingham Foot ...

Whole-cell vaccine was more effective than acellular vaccine during CA pertussis outbreak

Whole-cell pertussis vaccines were more effective at protecting against pertussis than acellular pertussis vaccines during a large recent outbreak, according to a new Kaiser Permanente study published in Pediatrics.

Commonly used catheters double risk of blood clots in ICU and cancer patients

Touted for safety, ease and patient convenience, peripherally inserted central catheters have become many clinicians' go-to for IV delivery of antibiotics, nutrition, chemotherapy, and other medications.

New theory on genesis of osteoarthritis comes with successful therapy in mice

Scientists at Johns Hopkins have turned their view of osteoarthritis (OA) inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, ...

Computational tool translates complex data into simplified 2-dimensional images

In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...

Researchers identify a potential new risk for sleep apnea: Asthma

Researchers at the University of Wisconsin have identified a potential new risk factor for obstructive sleep apnea: asthma. Using data from the National Institutes of Health (Heart, Lung, and Blood Institute)-funded Wisconsin ...