Protein regulation by monoubiquitin

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Abstract
Multi-ubiquitin chains target proteins for destruction by the proteasome. However, several proteins are monoubiquitylated. Recently, monoubiquitin has emerged as a regulator of the location and activity of diverse cellular proteins. Histone regulation: Core histones H2A and H2B and the linker histone H1 are monoubiquitylated. Ubiquitylation of histones is important for gene expression during meiosis and development. Endocytosis: Monoubiquitin serves as a signal to trigger the regulated internalization of plasma membrane proteins. Monoubiquitylation might also regulate the activity of components of the endocytic machinery. Virus budding: The retrovirus Gag polyprotein is monoubiquitylated and this modification is required for late stages of virus budding from infected cells. Surface regions of ubiquitin that are important for its different functions have been defined. One hydrophobic patch is promiscuous and is crucial for such diverse processes as proteasomal degradation and endocytosis. Another surface patch is important only for endocytosis and might have a role specifically in monoubiquitin functions. Modification with monoubiquitin might regulate protein location and activity in ways that are similar to modification with the ubiquitin-like proteins, SUMO-1, Rub1 and Apg12. Regulation of ubiquitin modification is important so that monoubiquitylated proteins are not inappropriately multi-ubiquitylated and degraded. Monoubiquitylation could be regulated by the activity of specific components of the ubiquitin machinery, by de-ubiquitylating enzymes, or by the presence or absence of positive and negative regulators of multi-ubiquitin chain assembly. Many more monoubiquitin proteins probably exist and remain to be identified. The mechanism by which monoubiquitin regulates substrate protein location and activity is a mystery that is the next big challenge for researchers in the field.