Evidence map›Paper›PMID 25510652›Full record

ArticleThe Biochemical journal2015

Unravelling the pivotal role of Alix in MVB sorting and silencing of the activated EGFR.

Sheng Sun, Xi Zhou, Wei Zhang, Gary E Gallick, Jian Kuang

Open access · greenAbstract read
In one paragraph

Article in The Biochemical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

25 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Therapeutically harnessing extracellular vesicles.Nature reviews. Drug discovery · 2022
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. The role of CHMP2BBrain research · 2016
    Review
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

5 authors at 1 institution in 1 country.

Sheng Sun*Department of Experimental Therapeutics, University of Texas, M.D. Anderson Cancer Center, Houston, Texas, U.S.A.
Xi Zhou*Department of Experimental Therapeutics, University of Texas, M.D. Anderson Cancer Center, Houston, Texas, U.S.A.
Wei Zhang‡The Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China.
Gary E Gallick†The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, U.S.A.
Jian Kuang*Department of Experimental Therapeutics, University of Texas, M.D. Anderson Cancer Center, Houston, Texas, U.S.A.
Beijing Normal University · CN

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 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 1 RO1 CA93941NCI NIH HHS CA-16672NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA093941
6 · The paper itself

Abstract

Endosomal sorting complex required for transport (ESCRT)-III-mediated membrane invagination and scission are a critical step in multivesicular body (MVB) sorting of ubiquitinated membrane receptors, and generally thought to be required for degradation of these receptors in lysosomes. The adaptor protein Alix is critically involved in multiple ESCRT-III-mediated, membrane-remodelling processes in mammalian cells. However, Alix knockdown does not inhibit degradation of the activated epidermal growth factor receptor (EGFR) in mammalian cell lines, leading to a widely held notion that Alix is not critically involved in MVB sorting of ubiquitinated membrane receptors in mammalian cells. In the present study, we demonstrate that, despite its non-essential role in degradation of the activated EGFR, Alix plays a critical role in its MVB sorting and silencing Epidermal growth factor (EGF) stimulation of mammalian cell lines induces Alix's interaction with the ubiquitinated EGFR via the Alix V domain, and increases Alix's association with membrane-bound charged multivesicular body protein 4 (CHMP4) via the Alix Bro1 domain. Under both continuous and pulse-chase EGF stimulation conditions, inhibition of Alix's interaction with membrane-bound CHMP4, inhibition of Alix dimerization through the V domain or Alix knockdown dramatically inhibits MVB sorting of the activated EGFR and promotes sustained activation of extracellular-signal regulated kinase (ERK)1/2. Under the continuous EGF stimulation conditions, these cell treatments also retard degradation of the activated EGFR. These findings indicate that Alix is critically involved in MVB sorting of ubiquitinated membrane receptors in mammalian cells.

Indexed as

Calcium-Binding ProteinsCell Cycle ProteinsEndosomal Sorting Complexes Required for TransportEpidermal Growth FactorErbB ReceptorsHEK293 CellsHumansMultivesicular BodiesUbiquitinationCalcium-Binding ProteinsCell Cycle ProteinsEGFR protein, humanEndosomal Sorting Complexes Required for TransportEpidermal Growth FactorErbB ReceptorsPDCD6IP protein, human

Identifiers

PMID25510652
PMCPMC4495973
OpenAlexW2043952539

What Socratic 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 Socratic graph.