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PMID: 10888670 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The APC11 RING-H2 finger mediates E2-dependent ubiquitination.

Molecular biology of the cell ·Vol. 11 ·No. 7 ·2000-07-00 ·Pages 2315-25

Leverson JD, Joazeiro CA, Page AM, Huang Hk, Hieter P, Hunter T

Abstract

Polyubiquitination marks proteins for degradation by the 26S proteasome and is carried out by a cascade of enzymes that includes ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). The anaphase-promoting complex or cyclosome (APC/C) comprises a multisubunit ubiquitin ligase that mediates mitotic progression. Here, we provide evidence that the Saccharomyces cerevisiae RING-H2 finger protein Apc11 defines the minimal ubiquitin ligase activity of the APC. We found that the integrity of the Apc11p RING-H2 finger was essential for budding yeast cell viability, Using purified, recombinant proteins we showed that Apc11p interacted directly with the Ubc4 ubiquitin conjugating enzyme (E2). Furthermore, purified Apc11p was capable of mediating E1- and E2-dependent ubiquitination of protein substrates, including Clb2p, in vitro. The ability of Apc11p to act as an E3 was dependent on the integrity of the RING-H2 finger, but did not require the presence of the cullin-like APC subunit Apc2p. We suggest that Apc11p is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiquitin to APC substrates in vivo.

MeSH Terms
Amino Acid Sequence Anaphase-Promoting Complex-Cyclosome Animals Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome Cell Survival Fungal Proteins/genetics,metabolism Humans Ligases/genetics,metabolism Molecular Sequence Data Saccharomyces cerevisiae/genetics,metabolism Ubiquitin-Conjugating Enzymes Ubiquitin-Protein Ligase Complexes Ubiquitin-Protein Ligases Ubiquitins/metabolism Zinc Fingers
Chemicals
Fungal Proteins Ubiquitins Ubiquitin-Conjugating Enzymes Ubiquitin-Protein Ligase Complexes ubiquitin-conjugating enzyme UBC4 ANAPC11 protein, human Anaphase-Promoting Complex-Cyclosome Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome Ubiquitin-Protein Ligases Ligases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Leverson J D
Molecular Biology and Virology Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Joazeiro C A
Page A M
Huang H k
Hieter P
Hunter T
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.11.7.2315
Published
2000-07-00
Pages
2315-25
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC14921
Subset
IM
Grants
NCI NIH HHS · CA 14185 · United States
NCI NIH HHS · CA 16519 · United States
NCI NIH HHS · T32 CA09523 · United States
NCI NIH HHS · P01 CA016519 · United States
NCI NIH HHS · T32 CA009523 · United States
External Links
PubMed source DOI: 10.1091/mbc.11.7.2315 PMC Full Text View journal details
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