Navigation Links
Study details regulation of vital tumor suppressor gene p53
Date:9/5/2007

(PHILADELPHIA) So vital is the p53 tumor suppressor gene in controlling cancer that its dysfunction is linked to more than half of human cancers. At the same time, the genes capacity for shutting down cell growth, even causing cells to commit suicide if necessary, is so absolute that it must be tightly regulated to maintain the optimal balance between protecting against cancer and permitting normal growth.

Now, a study by scientists at The Wistar Institute reveals new levels of subtlety in the bodys management of this all-important tumor suppressor gene and the protein it produces. The experiments show that, while the addition of a specific molecule at a particular site on the p53 protein prevents it from acting, the addition of a second copy of the same molecule at the same site reverses the effect, sending p53 into action. Further, removal of the second copy returns the protein to its repressed state.

In addition to the implications for understanding the activity of the p53 gene, the findings also outline an important new cycle of gene-regulating modifications involving the addition and removal of the molecules, called methyl groups, that may be widespread in the genome. A report on the study appears in the September 6 issue of Nature.

The p53 tumor suppressor is extremely potent in halting cell growth, says Shelley L. Berger, Ph.D., the Hilary Koprowski Professor at The Wistar Institute and senior author on the study. So, as critical as p53 is in protecting against the unchecked growth of cancer, you dont want it constantly on. If it were always on, your cells wouldnt be able to grow normally. Yet it needs to be constantly on call for activation against cancer and other aberrant cellular developments. Our study shows one way that the cell, working at one particular location on the p53 protein, maintains a nuanced but firm control over the genes activity.

Responsible for tumor suppression throughout the body, the p53 gene is mutated or otherwise disabled in a majority of human cancers. When working properly, the protein produced by the p53 gene acts by binding to DNA to activate other genes that direct cells with damaged DNA to cease dividing until the damage can be repaired. Cells with such damage include cancer cells, since all cancers track to genetic flaws of one kind or another, whether inherited or acquired. If repairs cannot be made, p53 commands the cells with damaged DNA to self-destruct so they are no longer a danger to the body.

This powerful ability of p53 to shut down cell division and induce cell death points to why fine-tuned regulatory mechanisms such as the one outlined in the new study are crucial for cellular survival.

In a previous study published in Nature in November 2006, Berger and her colleagues showed that the addition of a single methyl group a tiny molecule consisting of one carbon and three hydrogen atoms at a specific site on the p53 protein was sufficient to repress its activity. In the current study, the researchers found that the addition of a second methyl group at the same site reversed the effect. With the pair of methyl groups in place, the site is able to attract and bind a molecule called 53bp1, itself required for the p53 protein to bind to DNA to launch the genes responsible for carrying out its tumor-suppressing mission. With one methyl group in place, the site is said to be monomethylated; with two in place, it is dimethylated.

An important finding from our study is that the dimethylation mark is the required recognition site for 53bp1 on the p53 protein, says Jing Huang, Ph.D., lead author on the Nature study. If you remove that mark, 53bp1 cannot associate with the p53 protein, and p53s activity will be reduced.


'/>"/>

Contact: Franklin Hoke
hoke@wistar.org
215-898-3716
The Wistar Institute
Source:Eurekalert

Related medicine news :

1. Gene study links endometriosis, infertility
2. Study reveals how stress can make you sick
3. Study points out that HIV vaccine may not be accepted easily
4. A new study surpasses Gene Therapy Hurdle
5. Tomato Sauce reduces Cancer Risk- Study
6. A question on study of Adult Stem Cell
7. Study on obesity and heart failure
8. National Lung Study in the process
9. Marijuana gateway theory strengthened by study of twins
10. Old theory of adaptation confirmed by new study
11. Study casts doubt on keyboard ills
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/9/2016)... PA (PRWEB) , ... December 09, 2016 , ... "I ... Fla. "I used this old family recipe, which is meant to relieve gout and ... it gave me a 12-hour energy boost every time. It relieved what VA doctors ...
(Date:12/9/2016)... ... December 09, 2016 , ... The Holy ... in New York, NY, on December 3rd, to benefit Holy Name Medical Center's ... annual event, which raised over $1 million - the largest event in the ...
(Date:12/8/2016)... ... December 08, 2016 , ... The Florida Hospital ... and Hyperbaric Medical Society (UHMS), the leading authority in hyperbaric medicine. This accreditation ... a few hospitals and facilities have earned this distinction. This is the second ...
(Date:12/8/2016)... ... December 08, 2016 , ... Mirixa Corporation ... adherence, and other pharmacist-delivered patient care services, has announced the promotions of Karen ... to vice president of sales. , Litsinger joined Mirixa in 2008 after ...
(Date:12/8/2016)... ... December 08, 2016 , ... SunView ... customers and employees that are both engaging and easy to use. Coming off ... the software company revealed today its plans to roll out new AI-powered self-service ...
Breaking Medicine News(10 mins):
(Date:12/9/2016)... Fla. , Dec. 9, 2016  Harmar Mobility, LLC announced ... and a member of the Board of Directors. Photo ... ... Mr. Dawson,s ... development of organizations across a variety of industries. He brings to ...
(Date:12/9/2016)... -- Research and Markets has announced the addition of ... offering. ... global travel vaccines market to grow at a CAGR of 6.83% ... scenario and the growth prospects of the global travel vaccines market ... revenue generated from the sales of various vaccines administered to actively ...
(Date:12/8/2016)... -- IRIDEX Corporation (NASDAQ: IRIX ) today announced ... stock, $0.01 par value (the "Offering" with such shares being ... terms of the Offering will depend on market and other ... no assurance as to whether or when the Offering may ... proceeds it will receive from this offering for working capital ...
Breaking Medicine Technology: