Ubiquitin crosstalk connecting cellular processes

Abstract

The polypeptide ubiquitin is used in many processes as different as endocytosis, multivesicular body formation, and regulation of gene transcription. Conjugation of a single ubiquitin moiety is typically used in these processes. A polymer of ubiquitin moieties is required for tagging proteins for proteasomal degradation. Besides its role in protein degradation, ubiquitin is also engaged as mono- or polymer in intracellular signalling and DNA repair. Since free ubiquitin is present in limiting amounts in cells, changes in the demands for ubiquitin in any of these processes is likely to indirectly affect other ubiquitin modifications. For example, proteotoxic stress strongly increases poly-ubiquitylated proteins at the cost of mono-ubiquitylated histones resulting in chromatin remodelling and altered transcription. Here we discuss the interconnection between ubiquitin-dependent processes and speculate on the functional significance of the ubiquitin equilibrium as a signalling route translating cellular stress into molecular responses.

Figure 1

Ubiquitin: forms and functions. Free ubiquitin molecules are present in both the nucleus and the cytosol; the protein is small enough for passive diffusion through the nuclear pore between the two compartments. Ubiquitin conjugation to target proteins plays a central role in many processes of the cell. The best-known function of ubiquitin is its involvement in protein degradation via poly-ubiquitylation in the nucleus and cytoplasm. Mono-ubiquitylation of proteins has various functions depending on the target protein; it can vary from involvement in endocytosis at the plasma membrane, to DNA repair in the nucleus.

Figure 2

The ubiquitin cycle. Free ubiquitin plays a central role in the biochemistry of the cell; all processes that consume ubiquitin ultimately have to derive it from freely available ubiquitin. Because the amount of free ubiquitin is relatively small, processes that consume large amounts of ubiquitin will indirectly influence other cellular processes that depend on ubiquitin.