Ubiquitin-independent proteasomal degradation of tumor suppressors by human cytomegalovirus pp71 requires the 19S regulatory particle.

Abstract	Proteasomes generally degrade substrates tagged with polyubiquitin chains. In rare cases, however, proteasomes can degrade proteins without prior ubiquitination. For example, the human cytomegalovirus (HCMV) pp71 protein induces the proteasome-dependent, ubiquitin-independent degradation of the retinoblastoma (Rb) and Daxx proteins. These transcriptional corepressors and tumor suppressors inhibit the expression of cellular or viral genes that are required for efficient viral replication. Proteasomes are composed of a 20S catalytic core with or without one or two activator complexes, of which there are four different types. Here, we show that only one of these activators, the 19S regulatory particle that normally participates in ubiquitin-dependent protein degradation, is required for pp71-mediated degradation of Rb and Daxx. We report the unique use of a well-established route of substrate delivery to the proteasome by a viral protein to promote infection.
Authors	Laura L Winkler, Jiwon Hwang, Robert F Kalejta
Journal	Journal of virology (J Virol) Vol. 87 Issue 8 Pg. 4665-71 (Apr 2013) ISSN: 1098-5514 [Electronic] United States
PMID	23408605 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Adaptor Proteins, Signal Transducing Co-Repressor Proteins DAXX protein, human Molecular Chaperones Nuclear Proteins Retinoblastoma Protein Tumor Suppressor Proteins Viral Proteins cytomegalovirus phosphoprotein 71kDa Proteasome Endopeptidase Complex
Topics	Adaptor Proteins, Signal Transducing (metabolism) Animals Cell Line Co-Repressor Proteins Cytomegalovirus (pathogenicity) Humans Mice Molecular Chaperones Nuclear Proteins (metabolism) Proteasome Endopeptidase Complex (metabolism) Proteolysis Retinoblastoma Protein (metabolism) Tumor Suppressor Proteins (metabolism) Viral Proteins (metabolism)

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