Reference: Chen Q, et al. (2005) RNA interference toward UMP1 induces proteasome inhibition in Saccharomyces cerevisiae: evidence for protein oxidation and autophagic cell death. Free Radic Biol Med 38(2):226-34

Reference Help

Abstract

The proteasome is a large intracellular protease that is responsible for a large portion of intracellular proteolysis, in particular the degradation of a majority of short-lived and oxidized proteins. Inhibition of proteasome function occurs in response to multiple stressors, with proteasome inhibition sufficient for the induction of a wide range of cytotoxic processes. Although considerable advances have been made in the understanding of the proteasome, and the effects of proteasome inhibition, our understanding of these topics in Saccharomyces cerevisiae has been slowed by the inability of proteasome inhibitors to penetrate and/or be retained in S. cerevisiae. Expression of UMP1 is necessary for proteasome assembly in S. cerevisiae, and in the present study we examined the effectiveness of RNA interference for UMP1 as a means of achieving proteasome inhibition in S. cerevisiae. Induction of RNA interference for UMP1 resulted in a dramatic decrease in UMP1 at the protein level, which was not observed in cells transformed with control vector. RNA interference caused an impairment in proteasome function, and increase in protein oxidation, with proteins involved in both stress response and energy metabolism showing increased oxidation. Interestingly, RNA interference induced cell death that seemed to be autophagic in nature, suggesting possible cross talk between the proteasome and the autophagic proteolytic pathways. Taken together, these data indicate that RNA interference may be a useful model with which to study the effects of proteasome inhibition in S. cerevisiae and demonstrate the ability of proteasome inhibition to induce cytotoxic alterations in S. cerevisiae.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.
Authors
Chen Q, Ding Q, Thorpe J, Dohmen RJ, Keller JN
Primary Lit For
Additional Lit For
Review For

Interaction Annotations

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Type Assay Annotation Action Modification Phenotype Source Reference

Gene Ontology Annotations

Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Gene Ontology Term Qualifier Aspect Method Evidence Source Assigned On Annotation Extension Reference

Phenotype Annotations

Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Regulation Annotations

Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Experiment Assay Construct Conditions Strain Background Reference