Phosphorylation of Histone H2B as a Marker for Cell Proliferation and Differentiation in Development and Disease

BACKGROUND: Determining the cell cycle state of human cells can provide an important method for early detection of cancerous growth, especially the detection of cells at the G2/M phase of beginning cell division, or mitosis. However, current cell cycle detection methods cannot be correlated unambiguously with mitosis. Many cell cycle regulators are expressed during the entire cell cycle and are activated posttranslationally during cell division by modifications such as phosphorylation, so antibodies that recognize these proteins are not indicators. Furthermore, many cell cycle regulators carry several posttranslational modifications, and the primary sequence of these regulators is not phytogenetically conserved, so animal studies may not correlate with potential human indicators or targets. To date, antibodies that recognize modified or unmodified versions of the cell cycle regulators are not available.

DESCRIPTION: Scientists at the University of California and the University of Wisconsin have identified a novel histone modification, phosphorylation of serine 33 in histone H2B (H2B-S33), and have correlated this modification with transcriptional activation of the essential cell regulator string/Cdc25. String regulates cell cycle progression through G2/M phase. The presence of phosphorylated H2B (H2B-S33P) at the transcriptionally active string/cdc25 promoter provides a unique method and tool to determine the proliferative type and cell cycle status of cells. Such novel method is available for licensing as a diagnostic tool for identifying abnormal proliferating cells.

In addition, these scientists have developed proprietary monoclonal and polyclonal antibodies recognizing the phosphorylated H2B motif. These antibodies were raised against a recombinant Drosophila H2B peptide phosphorylated at serine 33, and named "anti-H2B-S33P." Anti-H2B-S33P recognizes the phosphorylated, evolutionarily-conserved motif in human cells, and can be used to determine the specific proliferation state of cells and tissues. Anti-H2B-S33P is available for licensing and represents a novel tool for cancer prognosis, diagnosis, and research.

APPLICATIONS & ADVANTAGES:

* Detection of H2B-S33P at the string/cdc25 promoter determines cell cycle progression, as string/cdc25 is exclusively expressed during G2/M phase. Furthermore, string/cdc25 is not transcribed in the absence of H2B-S33P despite the presence of other histone modifications at the string/cdc25 promoter. Thus, H2B-S33P represents a specific cell cycle marker.

* This H2B-S33P modification is phylogenetically conserved and can be used as a marker for cell cycle progression for both basic research with various animals and medical studies in humans.

* Detection of H2B-S33P at the string/cdc25 promoter provides the opportunity to determine the cell cycle state of human cells. Consequently, this method can be used for early detection of cancerous growth.

REFERENCE: 2004-474

Type of Offer: Licensing



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