title: 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: Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors: Laura L
authors: LL
authors: Winkler
authors: Jiwon
authors: J
authors: Hwang
authors: Robert F
authors: RF
authors: Kalejta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D056970:Co-Repressor Proteins; D003587:Cytomegalovirus / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D016160:Retinoblastoma Protein / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins; C051298:cytomegalovirus phosphoprotein 71kDa; D046988:Proteasome Endopeptidase Complex