The cytoskeleton is a scaffold upon which the cellular architecture is based. The euykaryotic cytoskeleton comprises actin filaments, microtubules and intermediate filaments. Intermediate filaments include the cytokeratins. Although their primary role is mechanical support, they are also mediators of subcellular distribution of other proteins and are involved in cell signalling pathways. Regulation of cytokeratin expression activity occurs in part through changes in post translational modification, including acetylation.

Histone deactylase inhibition by butyrate leads to hyperacetylation of proteins and modulation of gene expression in human cells through histone acetylation. The acetylation status of histones, and other proteins, is moderated by histone acetyl transferases (HATs) and histone deacetylases (HDACS); two classes of enzymes with opposing functions.

Whilst the acetylation of histones and a few other nuclear proteins has been known for some time, there is increasing realisation that acetylation of proteins is a widespread and potentially very important post-translational modification.

Researchers at the University of Sheffield have discovered that acetylation patterns of cytokeratins, in particular cytokeratins 8 and 18, can be correlated with cancer or a predisposition to cancer therefore raising the prospect of novel diagnostic tests and therapies. Cytokeratin 8 is also implicated in development of colon and other cancer and ulcerative colitis.

A patent application has been filed on acetylation patterns of cytokeratins, in particular cytokeratin 8 and/or 18 and the association of these patterns with cancer or a predisposition to cancer.

The patent covers:

• The use of cytokeratins 8 and/or 18 as diagnostic and/or prognostic tools for disease
• Therapeutic agents that modulate the acetylation state of cytokeratins 8 and/or 18
• A method to detect a histone deacetylase polypeptide in isolated samples.
  

There is the opportunity to develop this product as:

1. Diagnostic agents for ulcerative colitis, colon cancer and other cancer
2. Therapeutic agents for use against ulcerative colitis, colon cancer and other cancers
3. A progonostic tool for use against ulcerative colitis, colon cancer and other cancers.