Linked Life Data

20941496

Source:http://linkedlifedata.com/resource/pubmed/id/20941496

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-11-11
pubmed:abstractText
An rpn11-1 temperature-sensitive mutant shows defect in proteolysis, mitochondrial function and proteasome assembly. The Rpn11 protein is a proteasome subunit that deubiquitinates proteolytic substrates. Multiubiquitinated proteins interact with proteasome receptors, such as Rpn10, which intriguingly is also required for promoting proteasome stability. We report here that Rpn10 binds Rpn11, and genetic studies revealed synthetic lethality of an rpn11-1 rpn10? double mutant. The carboxy-terminus of Rpn11 is critical for function, as deletion of 7 C-terminal residues prevented suppression of rpn11-1 rpn10?. Native gel electrophoresis showed increased levels of the proteasome 20S catalytic particle in rpn11-1 rpn10?, and altered assembly. The inviability of rpn11-1 rpn10? was suppressed by rpn10(uim), a mutant that can bind the proteasome, but not multiubiquitin chains. rpn10(uim) reduced the levels of free 20S, and increased formation of intact proteasomes. In contrast, rpn10(vwa), which binds multiubiquitin chains but not the proteasome, failed to suppress rpn11-1 rpn10?. Moreover, high levels of multiubiquitinated proteins were bound to rpn10(vwa), but were not delivered to the proteasome. Based on these findings, we propose that the lethality of rpn11-1 rpn10? results primarily from altered proteasome integrity. It is conceivable that Rpn10/Rpn11 interaction couples proteasome assembly to substrate binding.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1432-0983
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
543-57
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Synthetic lethality of rpn11-1 rpn10? is linked to altered proteasome assembly and activity.
pubmed:affiliation
Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural