The role of MARCH1 in the ubiquitination and regulation of surface immunoreceptors

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We are trying to find ways in which cells in our body hide from our immune system, which may allow them to develop into cancers. To prevent a cell becoming cancerous and allow normal cell growth, all cells have receptors at their surface. These receptors need to be tightly controlled. The addition of small tags called ubiquitin onto these receptors causes their removal. Herpesviruses have devised ingenious ways of adding ubiquitin tags to important cell surface receptors, leading to the receptors’ removal. Viruses are cunning and stole this idea from our own cells. This led to the discovery of a new family of genes –called the MARCH family. We found that MARCHs play an important role in regulating receptors of our immune system. Our preliminary evidence suggests that MARCH proteins control immune cell activity to ensure that cells are neither over- nor under-active. We will use modern molecular techniques to find out how MARCH proteins control cell surface receptors.This will be important for learning about (i) how immune cells work (ii) whether MARCH proteins will be good drug targets to prevent immune-mediated disease and (iii) whether they allow cells to escape the immune system and develop into cancers.