Researchers from the Bhogaraju Group at EMBL Grenoble have gained new insights into how a cancer-relevant family of proteins bind their targets. The results of the study, published in The EMBO Journal, could potentially help in the development of drugs against certain chemotherapy- and radiotherapy-resistant cancers.
The Melanoma Antigen Gene (MAGE) family consists of more than 40 proteins in humans, most of which are only present in the testes under healthy conditions. However, in many cancers, these proteins are found in high levels in tissues where they are not usually expressed and are believed to play a role in promoting cancer progression.
One such MAGE protein – MAGEA4 – is known to interact with RAD18, a protein known to be abundant in some cancer cells. The latter is part of the molecular machinery that helps the cell repair damage to its DNA. High levels of RAD18 are responsible for the resistance of several cancers to genotoxic (DNA-damaging) chemotherapy or radiotherapy.
RAD18 functions by attaching little molecular tags – called ubiquitin – to different proteins. This tag, like a postal stamp, tells the cell what the fate of that protein would be. RAD18 can also attach this tag to itself – a process called autoubiquitination. This targets it for degradation, i.e. tells the cell to get rid of excess levels of this protein.
The Bhogaraju Group at EMBL Grenoble uses structural and cell biology-based approaches to study such ubiquitin-based pathways in normal physiology and disease. The team, in collaboration with the Hennig Group at EMBL Heidelberg, decided to look more deeply into the interaction between the proteins MAGEA4 and RAD18, using AlphaFold, an artificial-intelligence based tool that allows scientists to predict the structure of proteins.
About EMBL
EMBL is Europe’s flagship laboratory for the life sciences. Established in 1974 as an intergovernmental organisation, EMBL is supported by over 20 member states. EMBL performs fundamental research in molecular biology, studying the story of life. The institute offers services to the scientific community; trains the next generation of scientists and strives to integrate the life sciences across Europe. EMBL is international, innovative and interdisciplinary. Its more than 1700 staff, from over 80 countries, operate across six sites in Barcelona (Spain), Grenoble (France), Hamburg (Germany), Heidelberg (Germany), Hinxton (UK) and Rome (Italy). EMBL scientists work in independent groups and conduct research and offer services in all areas of molecular biology. EMBL research drives the development of new technology and methods in the life sciences. The institute works to transfer this knowledge for the benefit of society.
Researchers from the Bhogaraju Group at EMBL Grenoble have gained new insights into how a cancer-relevant family of proteins bind their targets. The results of the study, published in The EMBO Journal, could potentially help in the development of drugs against certain chemotherapy- and radiotherapy-resistant cancers. The Melanoma Antigen Gene (MAGE) family consists of more than 40 […]
