Proteins control most of the important reactions carried out within cells. It is widely recognised that the timely removal of proteins by protein destruction is easily as important as making proteins at the correct time. In humans when this process goes wrong the results are catastrophic for the individual causing a wide range of debilitating diseases such as cancer, Alzheimers and Parkinsons disease. Proteins are targeted for destruction by being marked by the addition of a ubiquitin chain. The chain acts as flag, which is recognised by the cell and the protein rapidly turned over by the 26S proteasome, which acts as a protein shredder. We study how the ubiquitin flag is recognised by the cell. Previously, we have identified a number of flag recognition proteins. We propose to carry out a number of experiments to investigate how these flag recognition proteins can interact with the flag adding machinery of the cell and then present the marked proteins for degradation by the 26S proteasome.||Recently, another protein flag called Nedd8 has been shown to be added to many different proteins. The function of Nedd8 addition to proteins is at present unclear but it is known that it does not target them for destruction. But as a substantial number of proteins seem to be modified in this way it seems that modification by this protein will have important implications for intracellular regulation. We propose to identify the different proteins modified by this protein flag and investigate how modification alters the properties of the protein.