Navigation Links
Moffitt Cancer Center researchers discover how cancer cells 'hijack' a mechanism to grow
Date:8/14/2012

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.

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.


'/>"/>

Contact: Kim Polacek
kim.polacek@moffitt.org
813-745-7408
H. Lee Moffitt Cancer Center & Research Institute
Source:Eurekalert

Related medicine news :

1. Moffitt researchers find cancer therapies affect cognitive functioning among breast cancer survivors
2. Moffitt Cancer Center researchers: Quality of life as important as quantity of life
3. Moffitt Cancer Center researchers working at frontiers of melanoma research
4. Moffitt researchers find adolescents with cancer concerned about their future reproductive health
5. Moffitt researcher publishes book on nutritional management of cancer treatment effects
6. Moffitt researcher awarded GE grant to develop tool to detect breast cancer metastasis genetic risks
7. Researchers creating designer lymph nodes based on Moffitts Total Cancer Care initiative
8. Moffitt Cancer Center researchers identify drivers of sarcoma growth and survival
9. Moffitt Cancer Center researchers develop and test new anti-cancer vaccine
10. Moffitt researcher, colleagues find success with new immune approach to fighting some cancers
11. Moffitt researchers: Darwins principles say cancer will always evolve to resist treatment
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/20/2017)... ... , ... Spectrum Aquatics Launches New ADA Portable Motion Trek BP 300 Lift. Built for durability, ... on wheels, it can be wheeled out of the way and stored when not in ... "We have transformed the feedback from customers into specific enhancements and created a new product ...
(Date:1/20/2017)... Boca Raton, FL (PRWEB) , ... January 20, 2017 , ... ... supplement development, announced it attended the January ECRM trade show to continue the marketing ... technologically advanced vitamin C supplement, known for providing 400 percent better absorption than traditional ...
(Date:1/20/2017)... ... January 20, 2017 , ... International Protein, a company based out of Australia ... attended the January ECRM trade show in Hilton Head, SC. , International Protein ... to create a line of products that would elevate her fitness regime. At this ...
(Date:1/20/2017)... , ... January 20, 2017 , ... “Mary Magdalene: Grace ... mysterious life of the woman who witnessed Jesus Christ firsthand. “Mary Magdalene: Grace is ... who spent her career as an educator interacting with countless women who had little ...
(Date:1/20/2017)... ... January 20, 2017 , ... D R Burton Healthcare Products ... was featured in a study indicating superior performance against competitive products in secretion ... Three Oscillating Positive Expiratory Pressure Devices During Simulated Breathing“ was published in the ...
Breaking Medicine News(10 mins):
(Date:1/19/2017)... Jan. 19, 2017  Stealth BioTherapeutics Inc. ( Stealth ... mitochondrial dysfunction, today announced new additions to its senior ... Chief Medical Officer, and Daniel Geffken as ... Jim Carr , Pharm.D. has been promoted to ... pleased to welcome Doug and Daniel to our management ...
(Date:1/19/2017)... 2017 According to a study conducted by ... to witness a CAGR of 6.5% during the forecast period 2016-2024. ... continue to be the leading market for cryotherapy globally during the ... Highlights ... ensuring affordable and adequate supply of gas in order to provide ...
(Date:1/19/2017)... Calif. , Jan. 19, 2017  Abaxis, Inc. ... manufacturing point-of-care blood analysis instruments and consumables for the ... call to discuss its financial results for the third ... call will be at 4:15 p.m. ET on Thursday, ... for the third quarter fiscal year 2017 after the ...
Breaking Medicine Technology: