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Citation
Nguyen, N.N., Rana, A., Goldman, C., Moore, R., Tai, J., Hong, Y., Shen, J., Walker, D.W., Hur, J.H. (2019). Proteasome β5 subunit overexpression improves proteostasis during aging and extends lifespan in Drosophila melanogaster.  Sci. Rep. 9(1): 3170.
FlyBase ID
FBrf0241665
Publication Type
Research paper
Abstract
The β5 subunit of the proteasome has been shown in worms and in human cell lines to be regulatory. In these models, β5 overexpression results in upregulation of the entire proteasome complex which is sufficient to increase proteotoxic stress resistance, improve metabolic parameters, and increase longevity. However, fundamental questions remain unanswered, including the temporal requirements for β5 overexpression and whether β5 overexpression can extend lifespan in other species. To determine if adult-only overexpression of the β5 subunit can increase proteasome activity in a different model, we characterized phenotypes associated with β5 overexpression in Drosophila melanogaster adults. We find that adult-only overexpression of the β5 subunit does not result in transcriptional upregulation of the other subunits of the proteasome as they do in nematodes and human cell culture. Despite this lack of a regulatory role, boosting β5 expression increases the chymotrypsin-like activity associated with the proteasome, reduces both the size and number of ubiquitinated protein aggregates in aged flies, and increases longevity. Surprisingly, these phenotypes were not associated with increased resistance to acute proteotoxic insults or improved metabolic parameters.
PubMed ID
PubMed Central ID
PMC6395709 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Sci. Rep.
    Title
    Scientific reports
    ISBN/ISSN
    2045-2322
    Data From Reference
    Alleles (3)
    Genes (13)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (1)
    Transgenic Constructs (3)