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

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