Mapping of Nuclear Export Signals and domains mediating aggregation of NBR1

Abstract

Autophagy is a conserved catabolic pathway for the lysosomal degradation of cytoplasmic components. Autophagy can be both selective and unselective. Selective autophagy receptor proteins are involved in mediating the degradation of specific substrates. Among these receptors we find the evolutionary related proteins p62 and NBR1, which are both involved in autophagic degradation of different ubiquitinated substrates. The p62 protein is known to shuttle between the nucleus and cytoplasm dependent on nuclear localization (NLS) and nuclear export sequences (NES). Here, we find that NBR1 harbors two active NES motifs. We also find that the subcellular distribution of NBR1 is dependent on its aggregation status and we map the location of the different domains responsible for aggregation of NBR1.