An unexpected player in a cancer defense system
November 28, 2011 in CancerResearchers 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 DNA is potentially very dangerous and linked to the development of cancer. 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 tumor suppressor 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 dementia 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 protein 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
Provided by
Karolinska Institutet
-
Molecular corkscrew
Nov 08, 2011 |
not rated yet |
0
-
Pathways that Can Repair Brca1 Cancer Gene Mutation Clarified in Mice
Apr 01, 2010 |
not rated yet |
0
-
New discovery linked to DNA repair and cancer
May 01, 2008 |
not rated yet |
0
-
Mutation linked to protein degradation underlies inherited ALS
Dec 08, 2010 |
not rated yet |
0
-
Researchers illuminate mechanisms that regulate DNA damage control and replication
Jan 05, 2009 |
not rated yet |
0
-
Of mice and mental models: Neuroscientific implications of risk-optimized behavior in the mouse
May 25, 2012 |
not rated yet |
0
-
Limits to growth: Scientists identify key metastasis-enabling enzyme
May 22, 2012 |
5 / 5 (4) |
0
-
Seeing is as seeing does: Spatially-structured retinal input in early development of cortical maps
Apr 26, 2012 |
5 / 5 (4) |
1
-
Dreamless nights: Brain activity during nonrapid eye movement sleep
Apr 09, 2012 |
4.4 / 5 (12) |
0
-
Take your time: Neurobiology sheds light on the superiority of spaced vs. massed learning
Mar 28, 2012 |
4.5 / 5 (21) |
3
-
Potential Breakthrough in Seizure Control
14 hours ago
-
Popping/Cracked sternum.
19 hours ago
-
Which Mental Illness Encompasses This Problem?
19 hours ago
-
A question about drug tolerance
May 23, 2012
-
Poor nutrition leading to overeating?
May 23, 2012
-
Math and dyslexia?
May 21, 2012
- More from Physics Forums - Medical Sciences
More news stories
Skp2 activates cancer-promoting, glucose-processing Akt
HER2 and its epidermal growth factor receptor cousins mobilize a specialized protein to activate a major player in cancer development and sugar metabolism, scientists report in the May 25 issue of Cell.
Cancer
May 25, 2012 |
not rated yet |
0
|
Pancreatectomy OK without downstaging from therapy
(HealthDay) -- Pancreatectomy improves median survival in pancreatic cancer patients even when presurgical neoadjuvant therapy does not lead to radiographic downstaging of tumors, according to a study published ...
Cancer
May 25, 2012 |
not rated yet |
0
Common therapies for basal cell carcinoma offer similar survival
(HealthDay) -- For patients with superficial basal cell carcinoma (sBCC), treatment with imiquimod or photodynamic therapy (PDT) results in similar long-term tumor-free survival, according to a review published ...
Cancer
May 25, 2012 |
not rated yet |
0
Cancer may require simpler genetic mutations than previously thought
Chromosomal deletions in DNA often involve just one of two gene copies inherited from either parent. But scientists haven't known how a deletion in one gene from one parent, called a "hemizygous" deletion, can contribute ...
Cancer
May 25, 2012 |
not rated yet |
0
|
New prostate cancer screening guidelines face a tough sell, study suggests
(Medical Xpress) -- Recent recommendations from the U.S. Preventive Services Task Force (USPSTF) advising elimination of routine prostate-specific antigen (PSA) screening for prostate cancer in healthy men are likely to encounter ...
Cancer
May 25, 2012 |
not rated yet |
1
Keep food safety in mind this memorial day weekend
(HealthDay) -- Picnics, parades and cookouts are as much a part of Memorial Day weekend as tributes to the United States' war veterans.
Travel to high altitudes tied to Crohn's, colitis flare-ups
(HealthDay) -- People with inflammatory bowel disease, which includes Crohn's disease and colitis, may be at increased risk for flare-ups when they fly or travel to high altitudes for skiing or mountain climbing, ...
Family history of Alzheimer's affects functional connectivity
(HealthDay) -- Cognitively normal individuals with a family history of late-onset Alzheimer's disease (AD) may display lower resting state functional connectivity in the default mode network (DMN) of the brain, ...
Transvaginal mesh op restores pelvic organ prolapse at price
(HealthDay) -- Transvaginal mesh (TVM) procedures are effective for anatomical restoration of pelvic organ prolapse (POP), but patients report a worsening of sexual function following surgery, according to ...
Of mice and mental models: Neuroscientific implications of risk-optimized behavior in the mouse
(Medical Xpress) -- Regardless of an organism’s biological complexity, every encephalized animal continuously makes under-informed behavioral choices that can have serious consequences. Despite its ubiquity, ...
Weight struggles? Blame new neurons in your hypothalamus
New nerve cells formed in a select part of the brain could hold considerable sway over how much you eat and consequently weigh, new animal research by Johns Hopkins scientists suggests in a study published in the May issue ...