Featured Research

from universities, journals, and other organizations

Protein Protects Anti-cancer Gene From Chemical Shutdown

Date:
July 20, 2007
Source:
University of Texas M. D. Anderson Cancer Center
Summary:
A protein that is largely absent in one type of skin cancer protects an important gene in a cell's defense against harmful mutations from being silenced, researchers report. In a series of experiments researchers show how IKK-alpha prevents silencing of the checkpoint gene by a chemical process known as methylation.

A protein that is largely absent in one type of skin cancer protects an important gene in a cell's defense against harmful mutations from being silenced, researchers at The University of Texas M. D. Anderson Cancer Center report in the July 20 edition of Molecular Cell.

Related Articles


The protein IKK-alpha, expressed at reduced levels in aggressive squamous cell carcinomas both in mice and humans, prevents a vital "checkpoint" gene from being chemically shut down, says Yinling Hu, Ph.D., senior author of the paper and assistant professor in M. D. Anderson's Department of Carcinogenesis at the Science Park - Research Division in Smithville, Texas.

Expression of the checkpoint gene, called 14-3-3-sigma, normally is triggered by the cancer-preventing gene p53 in response to DNA damage in the cell, Hu says. The protein expressed by the checkpoint gene helps to block a defective cell from dividing, allowing its genetic errors to be repaired rather than repeated in a new cell. Cells with damaged genes or genes that are behaving abnormally are the drivers of cancer.

"What we've identified is a mechanism that promotes genetic instability in keratinocytes, a critical type of skin cell that makes up 90 percent of epidermal cells, during the development of human skin cancers," Hu says. They found that the absence or weak expression of IKK-alpha leaves the checkpoint gene vulnerable to silencing.

In a series of experiments reported in the Molecular Cell paper, Hu and colleagues show how IKK-alpha prevents silencing of the checkpoint gene by a chemical process known as methylation. Methyl groups, consisting of a carbon atom surrounded by three hydrogen atoms, attach to specific locations on a gene and prevent it from expressing its protein without altering the gene. The team restored the checkpoint gene's activity by first restoring the expression of IKK-alpha in deficient cells by infecting the cells with a virus designed to express IKK-alpha.

"DNA methylation is largely responsible for shutting down the checkpoint gene expression in human cancer cells," Hu says. "Our finding opens a new avenue for identifying new therapeutic targets for battling cancer. Although IKK-alpha can protect the checkpoint gene 14-3-3-sigma from silencing, IKK-alpha itself is frequently impaired in cancer cells. So we are going to define specific downstream targets of IKK-alpha involved in regulating DNA methylation of the checkpoint gene. Those targets may be used to prevent silencing of the gene in cancer cells and so allow us to eliminate those cells."

In addition to understanding a critical component in skin cancer, the team notes that other researchers have shown that the checkpoint gene 14-3-3-sigma is silenced in a variety of other human epithelial cancers. Epithelial cells make up the outer layers of skin and the inner linings of many organs, including the lungs and the gastrointestinal, reproductive and urinary tracts.

The checkpoint gene had been known to be silenced by methylation, but the mechanism had not been understood. DNA methylation is known as an epigenetic process, because it affects a gene's activity without changing or damaging the gene itself.

Hu's research group has focused on IKK-alpha, which is an important component of a molecular complex that regulates the development of the lymph and immune systems. Hu and colleagues earlier showed that IKK-alpha is essential for embryonic skin development.

Co-authors with Hu are first author Feng Zhu, Ph.D., Xiaojun Xia, Ph.D., Bigang Liu, Jianjun Shen, Ph.D., and Yuhui Hu, all of M. D. Anderson's Science Park - Research Division; and Maria Person, Ph.D., of the Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin.

Research was funded by grants from the National Cancer Institute.


Story Source:

The above story is based on materials provided by University of Texas M. D. Anderson Cancer Center. Note: Materials may be edited for content and length.


Cite This Page:

University of Texas M. D. Anderson Cancer Center. "Protein Protects Anti-cancer Gene From Chemical Shutdown." ScienceDaily. ScienceDaily, 20 July 2007. <www.sciencedaily.com/releases/2007/07/070719122522.htm>.
University of Texas M. D. Anderson Cancer Center. (2007, July 20). Protein Protects Anti-cancer Gene From Chemical Shutdown. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2007/07/070719122522.htm
University of Texas M. D. Anderson Cancer Center. "Protein Protects Anti-cancer Gene From Chemical Shutdown." ScienceDaily. www.sciencedaily.com/releases/2007/07/070719122522.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) 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