Nuclear ubiquitin is poached for cytoplasmic protein degradation.

Ubiquitin (Ub) conjugation regulates numerous cellular processes, yet past biochemistry experiments suggested that although cells have a lot of Ub, little of it is free. On page 19, Dantuma et al. show that recruiting Ub to one site pulls it off another and, thus, Ub may link otherwise distinct processes, such as protein degradation and gene transcription.

GFP-Ub was evenly distributed in the nucleoplasm and appeared in many small foci in the cytoplasm. During photobleaching experiments, only a small fraction of the Ub diffused freely between the cytosol and the nucleus, indicating that most of it was conjugated to larger molecules. Moreover, about 70% of the Ub in the nucleus was immobile, consistent with its conjugation to histone H2A.

When GFP-Ub–expressing cells were exposed to proteotoxic stress, Ub translocated rapidly from the nucleus to the cytosol, and much of the cytoplasmic Ub moved at a rate consistent with conjugation to proteasome substrates. Simultaneously, H2A became increasingly deubiquitylated, causing chromatin condensation.

One possibility is that the cell simply cannot make enough Ub to satisfy its needs and must poach one Ub store in favor of another. However, the team hypothesizes that the cell relies on the limited pool of Ub to provide cross-talk between distant processes. For example, their preliminary data suggest that transcription levels may change in response to an accumulation of misfolded proteins.