New tumour suppressor action forms basis of chemo alternatives
how cells respond to DNA damage and other stresses that if
disrupted can cause cancer. The discovery could lead to new
diagnostic markers and cancer treatments with fewer side effects.
The discovery serves greater importance, as there is a need to identify alternative therapies, such as novel drugs that block signalling pathways that are abnormally activated. Such treatments could not only save lives but also eliminate the severe side effects caused by chemotherapy.
Often, the toxic nature of chemotherapy outweighs its intention in treating the cancer and there have been suggestions that this toxicity has contributed, if not been responsible, for the deaths of many cancer patients worldwide.
The findings, comprised of two reports, concentrated on the molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2.
The data, revealed the significance of the novel function of this recently discovered tumour-suppressive molecule, which is thought to inhibit cancer formation and growth.
The new mechanism regulates gene expression programs that allow for appropriate responses to DNA damage in normal cells.
When the process breaks down, such damage and other acute stresses are thought to lead to cancer.
"Our findings have established the mechanistic principles by which the inhibitor of growth 2 tumour suppressor recognizes chromatin and regulates cell growth, proliferation, stress responses and aging."
"We hope this discovery opens up new opportunities to establish novel targets to prevent and treat cancer," said Kutateladze, an assistant professor in the UCDHSC Department of Pharmacology.
The paper based on this work is the subject of the second report investigating the ING2 PHD domain links histone H3 lysine 4 methylation, which active gene repression.
Research in Kutateladze's laboratory focuses on molecular mechanisms underlying signaling and regulation by chromatin- and lipid-binding biomolecules implicated in cancer and other human diseases.
Kutateladze employed high field Nuclear Magnetic Resonance spectroscopy, X-ray crystallography and other biochemical and biophysical approaches to elucidate three-dimensional atomic-resolution structures and dynamics of proteins to better understand their physiological functions and relevance to diseases.
The two reports appear in the May 21 advanced online version of the journal >Nature.
