Apr 10, 2020

A role for the autophagic receptor, SQSTM1/p62, in trafficking NF-kB/RelA to nucleolar aggresomes

BioRxiv : the Preprint Server for Biology
I. T. LobbLesley Ann Stark


Elevated NF-kB activity is a contributory factor in many haematological and solid malignancies. Nucleolar sequestration of NF-kB/RelA represses this elevated activity and mediates apoptosis of cancer cells. Here we set out to understand the mechanisms that control the nuclear/nucleolar distribution of RelA and other regulatory proteins, so that agents can be developed that specifically target these proteins to the organelle. We demonstrate that RelA accumulates in intra-nucleolar aggresomes in response to specific stresses. We also demonstrate that the autophagy receptor, SQSTM1/p62, accumulates alongside RelA in these nucleolar aggresomes. This accumulation is not a consequence of inhibited autophagy. Indeed, our data suggest nucleolar and autophagosomal accumulation of p62 are in active competition. We identify a conserved motif at the N-terminus of p62 that is essential for nucleoplasmic-to nucleolar transport of the protein. Furthermore, using a dominant negative mutant deleted for this nucleolar localisation signal (NoLS), we demonstrate a role for p62 in trafficking RelA and other aggresome-related proteins to nucleoli. Together, these data identify a novel role for p62 in trafficking nuclear proteins to nucleolar aggreso...Continue Reading

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Mentioned in this Paper

Laboratory Procedures
Candidate Disease Gene
Health Information
Medical Subject Headings
Gene Ontology

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