(eLife Sciences Publications, Ltd, 2017) Whiteley, Alexandra; Prado, Miguel A; Peng, Ivan; Abbas, Alexander R; Haley, Benjamin; Paulo, Joao; Reichelt, Mike; Katakam, Anand; Sagolla, Meredith; Modrusan, Zora; Lee, Dong Yun; Roose-Girma, Merone; Kirkpatrick, Donald S; McKenzie, Brent S; Gygi, Steven; Finley, Daniel; Brown, Eric J
Ubiquilins (Ubqlns) are a family of ubiquitin receptors that promote the delivery of hydrophobic and aggregated ubiquitinated proteins to the proteasome for degradation. We carried out a proteomic analysis of a B cell lymphoma-derived cell line, BJAB, that requires UBQLN1 for survival to identify UBQLN1 client proteins. When UBQLN1 expression was acutely inhibited, 120 mitochondrial proteins were enriched in the cytoplasm, suggesting that the accumulation of mitochondrial client proteins in the absence of UBQLN1 is cytostatic. Using a Ubqln1−/− mouse strain, we found that B cell receptor (BCR) ligation of Ubqln1−/− B cells led to a defect in cell cycle entry. As in BJAB cells, mitochondrial proteins accumulated in BCR-stimulated cells, leading to protein synthesis inhibition and cell cycle block. Thus, UBQLN1 plays an important role in clearing mislocalized mitochondrial proteins upon cell stimulation, and its absence leads to suppression of protein synthesis and cell cycle arrest.
