Ubiquitination of non-protein substrates

The covalent attachment of ubiquitin is a common regulatory mechanism in various proteins. Although it has long been thought that the substrates of ubiquitination are limited to proteins, recent studies have changed this view: ubiquitin can be conjugated to lipids, sugars, and nucleotides. Ubiquitin is linked to these substrates by the action of different classes of ubiquitin ligases that have distinct catalytic mechanisms. Ubiquitination of non-protein substrates likely serves as a signal for the recruitment of other proteins to bring about specific effects. These discoveries have expanded the concept of ubiquitination and have advanced our insight into the biology and chemistry of this well-established modification process. In this review we describe the molecular mechanisms and roles of non-protein ubiquitination and discuss the current limitations.