Navigation Links
Cancer scientists determine mechanism of 1 of the most powerful tumor-suppressor proteins, Chd5
Date:1/10/2013

Cold Spring Harbor, NY A team of cancer researchers at Cold Spring Harbor Laboratory (CSHL) has solved the mystery of how one of the most powerful of the body's natural tumor-suppressing proteins, called Chd5, exerts its beneficial effects.

The findings, published online today in the journal Cell Reports, are important because Chd5 engages processes fundamental to cancer prevention. Conversely, when Chd5 is mutated or missing, an important door is opened to cancer initiation.

"For this reason, figuring out the mechanics of how Chd5 works to prevent cancer can directly impact the treatment of a diverse array of human cancers," says Alea A. Mills, Ph.D., team leader and Professor at CSHL. "Until now, we didn't understand very much about this process."

Since the time that Mills first discovered Chd5 as a tumor suppressor in 2007 and reported that it facilitates the expression of a tumor-suppressive network acting as a "master switch" for several tumor suppressor proteins Chd5 has been shown to predict survival following anticancer therapy. That is, patients struck with malignancies such as neuroblastoma, gall bladder cancer, and ovarian cancer live much longer if they have high levels of Chd5.

Now, Mills' team has discovered that Chd5's beneficial activity occurs when the protein binds to another protein called histone H3, which helps bundle the genetic material in the nucleus of cells.

Her team began their work knowing that Chd5 was a member of a family of proteins having at least nine members. Called chromatin remodeling proteins, they are involved in the immensely important job of shaping and chemically marking the highly compressed bundles of DNA and protein that biologists call chromatin.

Among other things, the degree to which chromatin is compressed helps determine whether particular genes among our total complement of 21,000 are either accessible or inaccessible to molecular machines that help to "express" them. Broadly speaking, tightly bundled chromatin is inaccessible to the gene-expression machinery, causing genes located in a given bundle to be shut off. The reverse is true of loosely packed chromatin.

The CSHL team's new finding involves Chd5's role in another process through which chromatin can be shaped and modified. Namely, via reading molecular groups on chromatin that effectively flag parts of its structure, a process called epigenetic marking.

Mills explains: "Our new work demonstrates that the Chd5 protein can activate the tumor-suppressive network when a portion of its structure (called PHD domains) bind to histone H3, one of the five histone proteins that make up the main structure of chromatin. Importantly, we found that this binding occurs specifically when the tail-like portion of histone H3 is what we call 'naked' that is, free of any epigenetic marks."

The team showed in living mice that when the gene that expresses Chd5 is mutated, yielding a protein that cannot bind the H3 histone, Chd5's usual tumor-suppressive effects do not occur; it no longer inhibits proliferation, thereby setting the stage for cancer initiation. The cancer used as a model for this part of the work was human neuroblastoma.

The team reported other details of the mechanism behind Chd5's tumor suppression, revealing how the interaction of Chd5 and naked H3 histones orchestrates programs that prevent cancer, mainly by binding to genes and affecting their "on" vs. "off" state.

"It is likely that Chd5's multi-faceted ways of enforcing tumor suppression will prove useful for regulating diverse types of cancers, including cancers with many different combinations of genetic lesions," Mills says.


'/>"/>

Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

Related medicine news :

1. Helping patients navigate new cancer drugs
2. Pap Test Could Spot Some Ovarian Cancers, Study Finds
3. High fiber diet prevents prostate cancer progression
4. Microscopic blood in urine unreliable indicator of urinary tract cancer
5. Common Heart Drug Might Improve Lung Cancer Survival
6. Hispanics leery of health care providers, often avoid cancer screenings, Moffitt study shows
7. UCSF Helen Diller Cancer Center awarded $36 million grant
8. Multiple sclerosis drug may one day treat colorectal cancer
9. Brief Life Expectancy Should Rule Out Certain Cancer Screenings: Study
10. US Drug Watchdog Now Urges Family Members Mourning The Loss Of A Loved One Who Developed Bladder Cancer After Using The Diabetes Drug Actos To Call The Johnson Law Group
11. ARUP Laboratories Introduces Blood Test to Aid in the Early Detection of Lung Cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... , ... June 27, 2016 , ... ... mental health professionals, announced today its affiliation with Tennessee Counseling Association. ... to the network of the Tennessee Counseling Association, adding exclusive benefits and promotional ...
(Date:6/26/2016)... ... June 27, 2016 , ... Quality metrics are proliferating in cancer ... they remain in the eye of the beholder, according to experts who offered insights ... American Journal of Managed Care. For the full issue, click here . , ...
(Date:6/26/2016)... ... 2016 , ... Brent Kasmer, a legally blind and certified personal trainer is helping to develop ... The fitness app plans to fix the two major problems leading the fitness industry today:, ... all type program , They don’t eliminate all the reasons people quit their ...
(Date:6/25/2016)... ... June 25, 2016 , ... The temporary closing of Bruton Memorial Library on June 21 ... brings up a new, often overlooked aspect of head lice: the parasite’s ability to live ... not a common occurrence, but a necessary one in the event that lice have simply ...
(Date:6/25/2016)... Oklahoma City, Oklahoma (PRWEB) , ... June 25, ... ... to helping both athletes and non-athletes recover from injury. Recently, he has implemented ... for the Oklahoma City area —Johnson is one of the first doctors to ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... PUNE, India , June 24, 2016 ... "Pen Needles Market by Type (Standard Pen Needles, Safety ... 12mm), Therapy (Insulin, GLP-1, Growth Hormone), Mode of Purchase ... published by MarketsandMarkets, This report studies the market for ... is expected to reach USD 2.81 Billion by 2021 ...
(Date:6/24/2016)... , Belgium , June 24, ... VNRX), today announced the appointment of Dr. ... Directors as a Non-Executive Director, effective June 23, ... Audit, Compensation and Nominations and Governance Committees.  As ... Futcher will provide independent expertise and strategic counsel ...
(Date:6/23/2016)... -- MedSource announced today that it has selected Datatrial,s ... choice.  This latest decision demonstrates MedSource,s commitment to ... by offering a state-of-the-art electronic data capture (EDC) ... the EDC platform of choice in exchange for ... long been a preferred EDC platform by our ...
Breaking Medicine Technology: