Dimerization quality control via ubiquitylation

Expanding the functional and structural repertoire of the proteome through protein dimerization is a fundamental concept in biology. Dimerization can occur in a homo- or heterotypic fashion with recurrent modular domains, such as BTB (BR-C, ttk, and bab) domains, leucine zippers, or coiled coils. Dimerization is a key factor in the regulation of enzymes, ion channels, receptors, and transcription factors. Indeed, proteomic studies indicate that a large fraction of mammalian proteins function only as dimers or multimers in cells (1). Thus, correct dimer formation is of fundamental importance for a healthy proteome and consequently for a healthy organism. However, whereas quality control systems for RNA, DNA, and the folding of nascent proteins are well-studied, whether and how correct composition of protein complexes is surveyed by cells has been unknown. On page 198 of this issue, Mena et al. (2) describe a quality control pathway that detects and eliminates nonfunctional dimer complexes. A failing dimerization quality control (DQC) pathway leads to the accumulation of aberrant dimers, which could contribute to the pathology of various diseases.