Hop/STIP1 depletion alters nuclear structure via depletion of nuclear structural protein emerin

Highlights: • The link between the co-chaperone Hop/STIP1 and nuclear protein emerin is studied. • Hop overexpression or depletion targets emerin for degradation. • Hop and emerin interact in complexes that do not require Hsp90, but accommodate Hsp70. • Nuclear structure is altered in Hop and emerin depleted cells. Hop/STIP1 is a co-chaperone of Hsp70 and Hsp90 that regulates a number of cell biology processes via interactions with cellular proteins. Here we report a new relationship between Hop and the nuclear structural protein emerin in maintenance of nuclear morphology. Depletion or overexpression of Hop resulted in the reduction of emerin protein levels via proteasomal and lysosomal pathways. Co-immunoprecipitation assays confirmed that Hop and emerin are in a common complex, which could accommodate Hsp70 but not Hsp90, and that TPR2AB is required for the association. Loss of Hop or emerin led to a deformation of nuclear structure, a statistically significant decrease in nuclear size, and was associated with changes in the levels of nuclear proteins, lamin A-C and fibrillarin. The nuclear defects upon Hop loss could be rescued by emerin overexpression. Taken together, these data suggest that Hop stabilises emerin and that loss of Hop alters nuclear structure via emerin degradation.