Evidence map›Paper›PMID 18722180›Full record

ArticleMolecular cell2008

The unique N terminus of the UbcH10 E2 enzyme controls the threshold for APC activation and enhances checkpoint regulation of the APC.

Matthew K Summers, Borlan Pan, Kiran Mukhyala, Peter K Jackson

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 104 citations in OpenAlex.

  1. Article
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  3. Ubiquitin-conjugating Enzymes in Cancer.International journal of biological sciences · 2026
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  12. Observational
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  15. Article
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  18. Neddylation E2 UBE2F Promotes the Survival of Lung Cancer Cells by Activating CRL5 to Degrade NOXA via the K11 Linkage.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
    Article
  19. Article
  20. Article

7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Matthew K SummersDepartment of Cellular Regulation, Genentech Inc., South San Francisco, CA 94080, USA.
Borlan PanDepartment of Protein Engineering, Genentech Inc., South San Francisco, CA 94080, USA.
Kiran MukhyalaDepartment of Bioinformatics, Genentech Inc., South San Francisco, CA 94080, USA.
Peter K JacksonDepartment of Cellular Regulation, Genentech Inc., South San Francisco, CA 94080, USA; Department of Pathology, Stanford University School of Medicine, Palo Alto, CA 94308, USA. Electronic address: pjackson@gene.com.
GenentechGenesys (United States) · US

Funding

TUMOR BIOLOGYT32CA009151 · NCI · STANFORD UNIVERSITY · PI CLEARY, MICHAEL L · 1985 to 2014
$5.5M
CYCLIN CONTROL OF DNA REPLICATIONR01GM054811 · NIGMS · STANFORD UNIVERSITY · PI JACKSON, PETER KENT · 1996 to 2005
$1.9M
Molecular Mechanisms of Drosophila Gonad MorphogenesisR01GM063023 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI VAN DOREN, MARK B · 2001 to 2005
$1.3M
A NOVEL F BOX PROTEIN REGULATING MITOSISR01GM060439 · NIGMS · STANFORD UNIVERSITY · PI JACKSON, PETER KENT · 2001 to 2004
$1.2M
NCI NIH HHS T32 CA009151NCI NIH HHS T32 CA09151NIGMS NIH HHS R01 GM054811NIGMS NIH HHS R01 GM060439NIGMS NIH HHS R01 GM063023
6 · The paper itself

Abstract

In vitro, the anaphase-promoting complex (APC) E3 ligase functions with E2 ubiquitin-conjugating enzymes of the E2-C and Ubc4/5 families to ubiquitinate substrates. However, only the use of the E2-C family, notably UbcH10, is genetically well validated. Here, we biochemically demonstrate preferential use of UbcH10 by the APC, specified by the E2 core domain. Importantly, an additional E2-E3 interaction mediated by the N-terminal extension of UbcH10 regulates APC activity. Mutating the highly conserved N terminus increases substrate ubiquitination and the number of substrate lysines targeted, allows ubiquitination of APC substrates lacking their destruction boxes, increases resistance to the APC inhibitors Emi1 and BubR1 in vitro, and bypasses the spindle checkpoint in vivo. Fusion of the UbcH10 N terminus to UbcH5 restricts ubiquitination activity but does not direct specific interactions with the APC. Thus, UbcH10 combines a specific E2-E3 interface and regulation via its N-terminal extension to limit APC activity for substrate selection and checkpoint control.

Indexed as

Amino Acid SequenceAnaphase-Promoting Complex-CyclosomeEnzyme ActivationEnzyme InhibitorsHeLa CellsHumansLysineMagnetic Resonance SpectroscopyMolecular Sequence DataProtein Structure, TertiaryStructure-Activity RelationshipSubstrate SpecificityUbiquitinationUbiquitin-Conjugating EnzymesUbiquitin-Protein Ligase ComplexesAnaphase-Promoting Complex-CyclosomeEnzyme InhibitorsLysineUBE2C protein, humanUbiquitin-Conjugating EnzymesUbiquitin-Protein Ligase Complexes

Identifiers

PMID18722180
PMCPMC2813190
OpenAlexW2057839247

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.