Cytomegalovirus sticks it to MHC

V iruses have numerous tricks for dodging the immune system. Stagg et al. reveal a key detail in one of these stratagems, identifying a protein that enables cyto-megalovirus to shut down an antiviral defense. Cytomegalovirus, which most people contract at some point in their lives, eludes immune system surveillance by targeting the protein MHC I. When we're sick, MHC I captures bits of viral proteins and presents them to cytotoxic T cells, which respond by killing cells that harbor the virus, stanching the infection. However, two cytomegalovirus genes dupe cells into ubiquitinating MHC I and demolishing it in the proteasome, the cellular garbage disposal. To trigger MHC I ubiquitination, the genes co-opt a cellular protein called the E3 ligase. Researchers haven't been able to pin down the identity of this protein, which could be one of several hundred enzymes. Stagg et al. sifted 373 candidates by depleting them one by one with RNAi. Knocking down a ligase called TRC8 spared MHC I from destruction, the team found. Mutant versions of TRC8 that curtail ubiquitination allow MHC I to return to duty. Researchers know little about the function of the protein except that it is mutated in some rare hereditary and sporadic kidney tumors. That could mean that one of the normal targets of TRC8 helps spur cancer. A dying epi-thelial cell doesn't receive tender treatment from its neighbors. They collaborate to evict it. Now, Slattum et al. reveal how epi-thelial layers force un-wanted cells to leave in a specifi c direction. An apoptotic cell sends a warning to its epithelial neighbors. They respond by weaving an intercellular band of actin and myosin that contracts, popping the cell out of the epithelial layer. By closing a potential gap, ejection maintains the layer's integrity. Banished cells can exit the layer from the upper, or apical, surface. Or they can leave from the basal surface, slipping into the underlying tissue. The benefi ts of basal ejection aren't clear—it might allow recycling of the cell. Slattum et al. probed another mystery about the process—what determines which way the cell departs. By labeling epithelial cells with tags that recognize only active myosin, the researchers discovered that the two exit routes require different contraction patterns. As little as 10% of the time, evicted cells leave basally. In those cases, only myosin in the upper portion of the surrounding cells clenches, pushing the apoptotic cell down. For …