Protein family hails Hypoxia breakthrough
7 Mar 2012 by Evoluted New Media
The discovery of a new family of proteins which regulate the body’s hypoxic response has allowed a significant step forward in understanding the process which can cause and affect the progress of many diseases.
The researchers – from Barts Cancer Institute at Queen Mary, University of London, and the University of Nottingham – have uncovered a previously unknown level of hypoxic regulation at a molecular level in human cells. This may provide a novel pathway for the development of new drug therapeutics to fight disease, like cancer.
“The results from this research represent a significant advancement in our understanding of precisely how the hypoxic response works,” said Dr Tyson Sharp, a molecular oncologist from Nottingham’s School of Biomedical Sciences.
“It will help researchers develop better drugs to fight cancer and also other human diseases that are caused by low levels of oxygen within our body, such as anaemia, myocardial infarction, stroke and peripheral arterial disease.”
Researchers discovered that LIM domain containing proteins, namely LIMD1, function as molecular scaffolds which bring together two key enzymes in the hypoxic response pathway – pyrol hydroxylases (PHD2) and von Hippel-Lindau (VHL) tumour suppressor.
Both PHD2 and VHL are involved in down-regulating the master regulator protein which responds to changes in intracellular oxygen – hypoxia-inducible factors or HIF-1.
When the hypoxic response malfunctions, loss of LIMD1 breaks down the bridge created between HD2 and VHL, and this enables HIF1 to function out of control and contribute to cancer formation.
Cancer cells have a faulty hypoxic response, and as the cells multiply they hijack the response to create their own rogue blood supply. This new blood supply allows the cancer to form large tumours, and to help the cancer spread to other parts of the body.
The work – funded by the Biotechnology and Biological Science Research Council (BBSRC) – is published in Nature Cell Biology. Further research is now being conducted at Barts Cancer Institute.
