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PMID: 24813613 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Enhanced protein degradation by branched ubiquitin chains.

Cell ·Vol. 157 ·No. 4 ·2014-05-08 ·Pages 910-21

Meyer HJ, Rape M

Abstract

Posttranslational modification of cell-cycle regulators with ubiquitin chains is essential for eukaryotic cell division. Such chains can be connected through seven lysine residues or the amino terminus of ubiquitin, thereby allowing the assembly of eight homogenous and multiple mixed or branched conjugates. Although functions of homogenous chain types have been described, physiological roles of branched structures are unknown. Here, we report that the anaphase-promoting complex (APC/C) efficiently synthesizes branched conjugates that contain multiple blocks of K11-linked chains. Compared to homogenous chains, the branched conjugates assembled by the APC/C strongly enhance substrate recognition by the proteasome, thereby driving degradation of cell-cycle regulators during early mitosis. Our work, therefore, identifies an enzyme and substrates for modification with branched ubiquitin chains and points to an important role of these conjugates in providing an improved signal for proteasomal degradation.

MeSH Terms
Anaphase-Promoting Complex-Cyclosome/metabolism HeLa Cells Humans NIMA-Related Kinases Proteasome Endopeptidase Complex/metabolism Protein Serine-Threonine Kinases/chemistry,metabolism Proteolysis Ubiquitin-Conjugating Enzymes/metabolism
Chemicals
Ube2S protein, human Ubiquitin-Conjugating Enzymes Anaphase-Promoting Complex-Cyclosome NEK2 protein, human NIMA-Related Kinases Protein Serine-Threonine Kinases Proteasome Endopeptidase Complex
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Meyer Hermann-Josef
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Rape Michael
Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: mrape@berkeley.edu.
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2014.03.037
Email
mrape@berkeley.edu
Published
2014-05-08
Pages
910-21
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC4028144
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01 GM083064 · United States
Corrections
CommentIn
PMID: 24813601
External Links
PubMed source DOI: 10.1016/j.cell.2014.03.037 PMC Full Text View journal details
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