Featured Research

from universities, journals, and other organizations

How cancer cells 'hijack' a mechanism to grow

Date:
August 14, 2012
Source:
H. Lee Moffitt Cancer Center & Research Institute
Summary:
Researchers have discovered a mechanism that explains how some cancer cells "hijack" a biological process to potentially activate cell growth and the survival of cancer gene expression.

Researchers at Moffitt Cancer Center and colleagues at the University of South Florida have discovered a mechanism that explains how some cancer cells "hijack" a biological process to potentially activate cell growth and the survival of cancer gene expression.

Related Articles


Their study appeared in a recent issue of Nature Structural & Molecular Biology.

The newly discovered mechanism involves histones (highly alkaline proteins found in cells that package and order DNA), and in this case, histone H2B, one of the five main histone proteins involved in the structure of chromatin. Chromatin is the combination of DNA and proteins that makes up the contents of the nucleus of a eukaryotic cell.

"Eukaryotic cells have evolved multiple mechanisms to maintain histone abundance at appropriate levels," said study lead author Nupam P. Mahajan, Ph.D., member of Moffitt's Molecular Oncology and Drug Discovery Program. "One of the best-studied mechanisms in higher eukaryotic cells is that the histone transcription or synthesis is switched off once a cell completes synthesis of DNA, however, how cells terminate histone synthesis is not fully clear."

The research team discovered that a modified histone itself regulates histone synthesis. The modification is histone H2B phosphorylation (in this case the process of adding a phosphate to a protein molecule) at tyrosine37 (tyrosine is one of 22 amino acids), which is critical for suppression of core histone mRNA synthesis. Additional experiments with mammalian and yeast cells have confirmed that the mechanism they discovered is widely operational and evolutionarily conserved.

The significance of this process in cancer cells became evident when they identified a tyrosine kinase, WEE1, as being a critical regulator of the process. Tyrosine kinases are enzymes that can transfer a phosphate group and can operate as "on/off" switches in many cell functions. Tyrosine kinases regulate critical cell processes, including cell growth, proliferation and differentiation.

"We identified WEE1 as the tyrosine kinase that phosporylates H2B in both mammal and yeast cells," explained Mahajan.

WEE1 protein levels are tightly regulated in cells, and its role in the cell cycle is well-established, Mahajan said. "What we discovered is that WEE1 is also a novel modifier of histone H2B, and inhibition, or knockdown, which resulted in a loss of H2B Tyr-phosporylation and an increase in the transcription of multiple core histone genes."

"Our data reveals a previously unknown mechanism by which Tyr-37 phosphorylation results in suppression of histone gene transcription activity," explained Mahajan. "Histone shutoff would lower histone transcript levels and eliminate overproduction of core histones."

According to the researchers, theirs is the first demonstration of Tyr-phosphorylated histone H2B and an evaluation of its function. The work also uncovers a previously unknown function of WEE1, a cell regulator that has a dual role in maintaining histone transcript levels.

According to the researchers, cancer cells would benefit ("unchecked" in growth and proliferation) by having lower levels of histone proteins. These lower histone levels would result in less compaction of chromatin (the combination of DNA and proteins making a cell's nucleus) and the expression of genes that might be otherwise kept "in check" in normal cells.

"Increased expression of WEE1 protein, shown in glioblastomas and triple-negative breast cancers, for example, indicates that cancer cells have 'hijacked' this mechanism to lower histone levels and thus activate the growth and survival of cancer cells," concluded the researchers.


Story Source:

The above story is based on materials provided by H. Lee Moffitt Cancer Center & Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kiran Mahajan, Bin Fang, John M Koomen, Nupam P Mahajan. H2B Tyr37 phosphorylation suppresses expression of replication-dependent core histone genes. Nature Structural & Molecular Biology, 2012; DOI: 10.1038/nsmb.2356

Cite This Page:

H. Lee Moffitt Cancer Center & Research Institute. "How cancer cells 'hijack' a mechanism to grow." ScienceDaily. ScienceDaily, 14 August 2012. <www.sciencedaily.com/releases/2012/08/120814100254.htm>.
H. Lee Moffitt Cancer Center & Research Institute. (2012, August 14). How cancer cells 'hijack' a mechanism to grow. ScienceDaily. Retrieved October 31, 2014 from www.sciencedaily.com/releases/2012/08/120814100254.htm
H. Lee Moffitt Cancer Center & Research Institute. "How cancer cells 'hijack' a mechanism to grow." ScienceDaily. www.sciencedaily.com/releases/2012/08/120814100254.htm (accessed October 31, 2014).

Share This



More Health & Medicine News

Friday, October 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

U.S. Ebola Response Measures Demonstrated

U.S. Ebola Response Measures Demonstrated

AP (Oct. 31, 2014) — Officials in the Washington area showed off Ebola response measures being taken at Dulles International Airport and the National Institutes of Health. (Oct. 31) Video provided by AP
Powered by NewsLook.com
Fauci Says Ebola Risk in US "essentially Zero"

Fauci Says Ebola Risk in US "essentially Zero"

AP (Oct. 30, 2014) — NIAID Director Anthony Fauci said the risk of Ebola becoming an epidemic in the U.S. is essentially zero Thursday at the Washington Ideas Forum. He also said an Ebola vaccine will be tested in West Africa in the next few months. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Nurse Defies Ebola Quarantine With Bike Ride

Nurse Defies Ebola Quarantine With Bike Ride

AP (Oct. 30, 2014) — A nurse who vowed to defy Maine's voluntary quarantine for health care workers who treated Ebola patients followed through on her promise Thursday, leaving her home for an hour-long bike ride. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Pot-Infused Edibles Raise Concerns in Colorado

Pot-Infused Edibles Raise Concerns in Colorado

AFP (Oct. 30, 2014) — Colorado may have legalized marijuana for recreational use, but the debate around the decision still continues, with a recent - failed - attempt to ban cannabis-infused edibles. Duration: 01:53 Video provided by AFP
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