November 2, 2024

Groundbreaking Research on MAGE Proteins Offers New Hope for Resistant Cancers

In many cancers, these proteins are discovered in high levels in tissues where they are not generally expressed and are thought to play a function in promoting cancer progression.One such MAGE protein– MAGEA4– is understood to interact with RAD18, a protein understood to be abundant in some cancer cells. 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 researchers to anticipate the structure of proteins.The team, which included Bhogaraju Group PhD trainee Simonne Griffith-Jones and postdoc Urbi Mukhopadhyay, found that MAGEA4 has a groove that can bind an area of the RAD18 protein, which prevents the latter from attaching ubiquitin groups to itself and subsequently getting degraded.Interestingly, the researchers might use a short artificial protein fragment, simulating the part of RAD18 that binds the groove in MAGEA4, to obstruct the interaction between the two proteins. In addition to the groove, the researchers likewise observed that 2 parts within the RAD18 protein connect with each other, which assists it attach the ubiquitin tag to a protein which promotes cancer cell survival.

In many cancers, these proteins are found in high levels in tissues where they are not typically revealed and are believed to play a function in promoting cancer progression.One such MAGE protein– MAGEA4– is known to engage with RAD18, a protein known to be plentiful in some cancer cells. The team, in partnership with the Hennig Group at EMBL Heidelberg, chose to look more deeply into the interaction between the proteins MAGEA4 and RAD18, using AlphaFold, an artificial-intelligence-based tool that enables researchers to anticipate the structure of proteins.The team, which included Bhogaraju Group PhD trainee Simonne Griffith-Jones and postdoc Urbi Mukhopadhyay, discovered that MAGEA4 has a groove that can bind a section of the RAD18 protein, which avoids the latter from connecting ubiquitin groups to itself and subsequently getting degraded.Interestingly, the scientists might use a short artificial protein piece, mimicking the part of RAD18 that binds the groove in MAGEA4, to block the interaction between the 2 proteins. In addition to the groove, the scientists likewise observed that two parts within the RAD18 protein engage with each other, which assists it connect the ubiquitin tag to a protein which promotes cancer cell survival.