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PMID: 12626766 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Proteasome-dependent, ubiquitin-independent degradation of the Rb family of tumor suppressors by the human cytomegalovirus pp71 protein.

Kalejta RF, Shenk T

Abstract

Most of the substrates degraded by the proteasome are marked with polyubiquitin chains. However, there are a limited number of examples of nonubiquitinated proteins that are degraded by the proteasome. Here, we describe the degradation of the retinoblastoma family of tumor suppressor proteins by the proteasome in the absence of polyubiquitination. The retinoblastoma protein (p105), p107, and p130 are each targeted for degradation by the pp71 protein, which is encoded by the UL82 gene of human cytomegalovirus. It functions to direct their degradation in the absence of other viral proteins. While the pp71-mediated degradation of the retinoblastoma family of proteins requires proteasome function, it occurs without the attachment of ubiquitin to the substrates and in the absence of a functioning ubiquitin-conjugation system.

MeSH Terms
Animals Cell Line Cysteine Endopeptidases/metabolism Cytomegalovirus/genetics,metabolism Humans Mice Multienzyme Complexes/metabolism Mutation Nuclear Proteins/metabolism Phosphoproteins/metabolism Proteasome Endopeptidase Complex Proteins Recombinant Proteins/genetics,metabolism Retinoblastoma Protein/metabolism Retinoblastoma-Like Protein p107 Retinoblastoma-Like Protein p130 Temperature Transfection Ubiquitin/metabolism Viral Proteins/genetics,metabolism
Chemicals
Multienzyme Complexes Nuclear Proteins Phosphoproteins Proteins RBL1 protein, human RBL2 protein, human Rbl1 protein, mouse Rbl2 protein, mouse Recombinant Proteins Retinoblastoma Protein Retinoblastoma-Like Protein p107 Retinoblastoma-Like Protein p130 Ubiquitin Viral Proteins cytomegalovirus phosphoprotein 71kDa Cysteine Endopeptidases Proteasome Endopeptidase Complex
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kalejta Robert F
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Shenk Thomas
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2003-03-18
Epub
2003-00-07
Pages
3263-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC152280
Subset
IM
Grants
NCI NIH HHS · R01 CA082396 · United States
NCI NIH HHS · CA 82396 · United States
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