Evidence map›Paper›PMID 27462417›Full record

ArticleCell discovery2015

ALG-2 activates the MVB sorting function of ALIX through relieving its intramolecular interaction.

Sheng Sun, Xi Zhou, Joe Corvera, Gary E Gallick, Sue-Hwa Lin, Jian Kuang

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Cell discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

26 citing papers in PubMed, 37 citations in OpenAlex.

  1. Lysosomal homeostasis at the crossroads of neurodegeneration.The Journal of clinical investigation · 2026
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  2. Mitochondrial proteostasis regulated by CRL5Communications biology · 2025
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  11. In vitro reconstitution of calcium-dependent recruitment of the human ESCRT machinery in lysosomal membrane repair.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  12. Bro1 family proteins harmonize cargo sorting with vesicle formation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Amino Acid Deletions in p6International journal of molecular sciences · 2020
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Sheng SunDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA.
Xi ZhouDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
Joe CorveraA&G Pharmaceuticals, Inc. , Baltimore, MD, USA.
Gary E GallickThe University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sue-Hwa LinThe University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA; Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jian KuangDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA.
The University of Texas MD Anderson Cancer Center · USA&G Pharmaceutical (United States) · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Effects of DNA Damaging Agents on G2 Phase CheckpointR01CA093941 · NCI · UNIVERSITY OF TEXAS MD ANDERSON CAN CTR · PI KUANG, JIAN · 2002 to 2005
$998k
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA093941
6 · The paper itself

Abstract

The modular adaptor protein ALIX is critically involved in endosomal sorting complexes required for transport (ESCRT)-mediated multivesicular body (MVB) sorting of activated epidermal growth factor receptor (EGFR); however, ALIX contains a default intramolecular interaction that renders ALIX unable to perform this ESCRT function. The ALIX partner protein ALG-2 is a calcium-binding protein that belongs to the calmodulin superfamily. Prompted by a defined biological function of calmodulin, we determined the role of ALG-2 in regulating ALIX involvement in MVB sorting of activated EGFR. Our results show that calcium-dependent ALG-2 interaction with ALIX completely relieves the intramolecular interaction of ALIX and promotes CHMP4-dependent ALIX association with the membrane. EGFR activation induces increased ALG-2 interaction with ALIX, and this increased interaction is responsible for increased ALIX association with the membrane. Functionally, inhibition of ALIX activation by ALG-2 inhibits MVB sorting of activated EGFR as effectively as inhibition of ALIX interaction with CHMP4 does; however, inhibition of ALIX activation by ALG-2 does not affect cytokinetic abscission or equine infectious anemia virus (EIAV) budding. These findings indicate that calcium-dependent ALG-2 interaction with ALIX is specifically responsible for generating functional ALIX that supports MVB sorting of ubiquitinated membrane receptors.

Indexed as

ALG-2ALIXCHMP4EGFRMVB sorting

Identifiers

PMID27462417
PMCPMC4860835
OpenAlexW2475087632

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.