Quality control of cytoplasmic proteins inside the nucleus

A complex network of molecular chaperones and proteolytic machinery safeguards the proteins which comprise the proteome, from the time they are synthesized on ribosomes to their destruction via prote-olysis. Impaired protein quality control results in the accumulation of aberrant proteins, which may undergo unwanted spurious interactions with other proteins, thereby interfering with a broad range of cellular functions. To protect the cellular environment, such proteins are degraded or sequestered into inclusions in different subcellular compartments. Recent findings demonstrate that aberrant or mistar-geted proteins from different cytoplasmic compartments are removed from their environment by trans-porting them into the nucleus. These proteins are degraded by the nuclear ubiquitin-proteasome system or sequestered into intra-nuclear inclusions. Here, we discuss the emerging role of the nucleus as a cel-lular quality compartment based on recent findings in the yeast Saccharomyces cerevisiae. We describe the current knowledge on cytoplasmic substrates of nuclear protein quality control, the mechanism of nuclear import of such proteins, as well as possible advantages and risks of nuclear sequestration of aber-rant proteins. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).

Automated summary

The nucleus plays an emerging role in cellular quality control by degrading or sequestering aberrant proteins, thus protecting the cellular environment.