We study MHC I molecules and other critical cell surface receptors. We showed that the cancer-causing herpesviruses (KSHV) pirated ubiquitin E3 ligases from their vertebrate hosts. These ligases ubiquitinate and downregulate critical cell surface receptors and teach us about receptor regulation, required for all growth factor receptors. Indeed E3 ligases have emerged as an important means of regulating receptor cell surface expression ? critical in many forms of human cancer. Our laboratory studies: (i)mechanisms used by viruses to evade immune recognition, particularly MHC class I molecules. (ii)the role of ubiquitin in the regulation of cell surface receptors, including the use of siRNA screens to identify the key enzymes of the ubiquitination pathway regulating these receptors. (iii)the use of quantitative proteomics (SILAC) to probe cell surface receptor regulation. (iv)components of the endosomal sorting machinery used by internalised, ubiquitinated cell surface receptors.