(Press-News.org) 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.
###
About Moffitt Cancer Center
Located in Tampa, Moffitt is one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt's excellence in research, its contributions to clinical trials, prevention and cancer control. Since 1999, Moffitt has been listed in U.S. News & World Report as one of "America's Best Hospitals" for cancer. With more than 4,200 employees, Moffitt has an economic impact on the state of nearly $2 billion. For more information, visit MOFFITT.org, and follow the Moffitt momentum on Facebook, twitter and YouTube.
Media release by Florida Science Communications
END
VIDEO:
Researchers at the La Jolla Institute for Allergy & Immunology have identified the specific type of immune cells that orchestrate the inflammatory attack on the artery wall, which is a...
Click here for more information.
SAN DIEGO – (August 14, 2012) – Most people probably know that heart disease remains the nation's No. 1 killer. But what many may be surprised to learn is that cholesterol has a major accomplice in causing dangerous arterial plaque buildup that can ...
Whilst the most powerful earthquake since records began hit Japan in 2011, triggering a massive tsunami which devastated much of the country, space scientists involved in one of the 'brightest' international Sun missions continued working tirelessly at the Institute of Space and Astronautical Science in Sagamihara, Japan, to capture new data from our turbulent star.
These latest Hinode results, to be discussed in a meeting at the University of St Andrews this week (Tuesday 14 August), include new data on the structure of the Sun's coronal magnetic field, obtained whilst ...
Guided press tour
The excavation will be open to the press on Wednesday 15 August from 13.00 to 15.30.The tour starts at Alkenvej 171, 8660 Skanderborg.
...
Sulphur dioxide emissions from shipping have sharply decreased in EU ports thanks to an EU policy which limits sulphur content in fuels for ships at berth or at anchor in ports. Scientists at the European Commission's Joint Research Centre measured key air quality parameters in Mediterranean harbours before and after the entry into force of the low-sulphur requirements in January 2010. In European harbours they found an average decrease of 66% in concentrations of sulphur dioxide, a chemical compound that poses risks to health and the environment. Measurements taken in ...
People who give positive encouragement and constructive criticism could be wasting their breath according to the latest research from a psychology expert at Queen Mary, University of London.
The study, published in the journal Frontiers in Neuroscience, found that when people received either positive or negative feedback about their performance on complex decision-making tasks, it made their decision making worse.
Study author Dr Magda Osman explained: "The kind of task people had to perform was difficult and demanding. So, when people received positive or negative ...
The mammalian skull, including that of people, is composed of about 20 bones. Fish, reptile and bird skulls, however, have considerably more. After all, when mammals evolved from reptile-like vertebrates 320 million years ago, the skull's structure became simplified during its development and the number of skull bones decreased.
Some bones were lost in the lineage leading to mammals in the course of evolution, especially a number of skull roof bones. The skull's interparietal, which is one of the skull roof bones, particularly puzzled researchers: on the one hand, it ...
They're sleek. They're fast. They're powerful. And, they are deafening. Furthermore, those Top Gun military jets need to be up in the air in the wee hours – over land – to simulate their landings on aircraft carriers. But innovations out of the University of Cincinnati's Gas Dynamics and Propulsion Laboratory are showing promise in reducing the intense noise of these supersonic jets without impacting their power. It's research that can help neighborhoods slumber a little more soundly, keep their windows rattling a little less loudly and also protect the hearing of military ...
University of Cincinnati research – from noise reduction in sophisticated military jets to quieter car rides – will be presented at INTER-NOISE 2012, the 41st International Congress and Exposition on Noise Control Engineering, to be held Aug. 19-22 in New York City. UC is among only a few universities with a specific focus on vehicle noise control.
The UC research to be presented at INTER-NOISE:
UC innovations to reduce the noise of the nation's most sophisticated military aircraft. Jeff Kastner, research assistant professor in the UC College of Engineering and Applied ...
All noise is not necessarily equal – especially when it comes to sound minimization in automobiles.
For instance, automakers have long used sound-absorbing materials (passive control) in the design of cars in order to minimize engine noise and the "routine" noise of tires traveling on smooth pavement at a consistent speed. However, a means to minimize sudden, unexpected noises – like those from an encounter with potholes, bumps or other roadway pavement obstacles – has been more problematic.
A significant step in countering such unexpected roadway noises is the development ...
Until recent decades the Atlantic Rainforest covered a large area of today's Brazil from Amazonas to present-day Argentina. In the 1970s, after years of deforestation, this rain forest was almost completely destroyed, mainly replaced by cattle pastures. This study reveals an unexpected aspect of deforestation. Thorsten Dittmar's team and colleagues from Brazil and the USA show that the common practice of slash and burn left huge amounts of charcoal in the soil. This charcoal is washed out by rainfalls and transported by rivers into the Atlantic Ocean. The soluble fraction ...
