New tumour suppressor in mitochondria
Successful treatment of cancers relies on agents such as radiation and chemotherapeutic drugs that cause DNA damage and lead to apoptosis or programmed cell death. Ironically, apoptosis represents a control mechanism necessary for the efficient function of any multicellular organism whereby old or malfunctioning cells are destroyed. There are however instances when tumours are resistant to treatment using apoptotic pathways. The biochemical explanation for this is the presence of a blockage in the route to cell self-destruction. Related to this, as part of their multiplication control, cells are equipped with several systems but when these cease to work properly, uncontrolled cell growth occurs. One of these involves the alternative reading frame (ARF) protein. This is almost exclusively nuclear in its situation and it works together with the p53 proteins to inhibit the stimulation of cell growth and division. As part of IMPALED, an EU-funded project, researchers investigated new therapies for cancer based on the molecular interactions in these apoptotic pathways. More specifically, partners at the Weizmann Institute of Science focused their research on a new form of tumour suppressor, this time localised in the mitochondria. Aptly named, short mitochondrial ARF (smARF) is smaller than its nuclear counterpart. Another difference is it does not require the presence of the p53 protein to fulfil its regulatory role. SmARF acts directly on the membrane potential of the mitochondrion, the effect of which is to trigger slow cell death. This work represents yet another strand in the research into the control of apoptosis and its link with tumour development and sensitivity to treatment. Results of the research of the project as a whole have been published as experimental papers and review articles in peer-review journals. One of the ultimate goals is the commercialisation of promising cancer treatments.