Proteasome activator Blm10 levels and autophagic degradation directly impact the proteasome landscape

J Biol Chem. 2021 Jan-Jun:296:100468. doi: 10.1016/j.jbc.2021.100468. Epub 2021 Feb 25.

Abstract

The proteasome selectively degrades proteins. It consists of a core particle (CP), which contains proteolytic active sites that can associate with different regulators to form various complexes. How these different complexes are regulated and affected by changing physiological conditions, however, remains poorly understood. In this study, we focused on the activator Blm10 and the regulatory particle (RP). In yeast, increased expression of Blm10 outcompeted RP for CP binding, which suggests that controlling the cellular levels of Blm10 can affect the relative amounts of RP-bound CP. While strong overexpression of BLM10 almost eliminated the presence of RP-CP complexes, the phenotypes this should induce were not observed. Our results show this was due to the induction of Blm10-CP autophagy under prolonged growth in YPD. Similarly, under conditions of endogenous BLM10 expression, Blm10 was degraded through autophagy as well. This suggests that reducing the levels of Blm10 allows for more CP-binding surfaces and the formation of RP-CP complexes under nutrient stress. This work provides important insights into maintaining the proteasome landscape and how protein expression levels affect proteasome function.

Keywords: Blm10; autophagy; proteasome; proteasome storage granule; protein degradation; stress response; ubiquitin; yeast.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Autophagy / genetics
  • Autophagy / physiology
  • Cytoplasm
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Processing, Post-Translational
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Blm10 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Proteasome Endopeptidase Complex