Evidence map›Paper›PMID 27621469›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

PtdIns(4,5)P2 signaling regulates ATG14 and autophagy.

Xiaojun Tan, Narendra Thapa, Yihan Liao, Suyong Choi, Richard A Anderson

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 6% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.

  1. Guideline
  2. Review
  3. The ATG14: multi-layer autophagy control and an emerging therapeutic target in cancer.Apoptosis : an international journal on programmed cell death · 2026
    Review
  4. Local PI(4,5)PNature communications · 2026
    Article
  5. Review
  6. Article
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  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
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  15. Article
  16. TSPO protein binding partners in bacteria, animals, and plants.Journal of bioenergetics and biomembranes · 2021
    Review
  17. Article
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  20. 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.

Xiaojun TanProgram in Molecular and Cellular Pharmacology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706.ORCID 0000-0003-3300-2240
Narendra ThapaProgram in Molecular and Cellular Pharmacology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706.
Yihan LiaoProgram in Molecular and Cellular Pharmacology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706.
Suyong ChoiProgram in Molecular and Cellular Pharmacology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706.
Richard A AndersonProgram in Molecular and Cellular Pharmacology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 raanders@wisc.edu.
University of Wisconsin–Madison · US

Funding

Targeting of Phosphoinositide Signaling in Migration, Invasion and MetastasisR01GM057549 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI ANDERSON, RICHARD A. · 1998 to 2019
$5.7M
PI Signaling Role in Epithelial/Mesenchymal TransitionR01CA104708 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI ANDERSON, RICHARD A. · 2004 to 2014
$2.9M
NCI NIH HHS R01 CA104708NIGMS NIH HHS R01 GM057549
6 · The paper itself

Abstract

Autophagy is a regulated self-digestion pathway with fundamental roles in cell homeostasis and diseases. Autophagy is regulated by coordinated actions of a series of autophagy-related (ATG) proteins. The Barkor/ATG14(L)-VPS34 (a class III phosphatidylinositol 3-kinase) complex and its product phosphatidylinositol 3-phosphate [PtdIns(3)P] play key roles in autophagy initiation. ATG14 contains a C-terminal Barkor/ATG14(L) autophagosome-targeting sequence (BATS) domain that senses the curvature of PtdIns(3)P-containing membrane. The BATS domain also strongly binds PtdIns(4,5)P2, but the functional significance has been unclear. Here we show that ATG14 specifically interacts with type Iγ PIP kinase isoform 5 (PIPKIγi5), an enzyme that generates PtdIns(4,5)P2 in mammalian cells. Autophagosomes have associated PIPKIγi5 and PtdIns(4,5)P2 that are colocalized with late endosomes and the endoplasmic reticulum. PtdIns(4,5)P2 generation at these sites requires PIPKIγi5. Loss of PIPKIγi5 results in a loss of ATG14, UV irradiation resistance-associated gene, and Beclin 1 and a block of autophagy. PtdIns(4,5)P2 binding to the ATG14-BATS domain regulates ATG14 interaction with VPS34 and Beclin 1, and thus plays a key role in ATG14 complex assembly and autophagy initiation. This study identifies an unexpected role for PtdIns(4,5)P2 signaling in the regulation of ATG14 complex and autophagy.

Indexed as

AutophagyAdaptor Proteins, Vesicular TransportAutophagy-Related Protein 5Autophagy-Related ProteinsBeclin-1Carrier ProteinsCell LineEndoplasmic ReticulumEndosomesGene Knockdown TechniquesHumansMutationPhosphatidylinositol 4,5-DiphosphatePhosphotransferases (Alcohol Group Acceptor)Protein BindingProtein DomainsAdaptor Proteins, Vesicular TransportATG14 protein, humanAutophagy-Related Protein 5Autophagy-Related ProteinsBeclin-1Carrier ProteinsPhosphatidylinositol 4,5-DiphosphatePhosphotransferases (Alcohol Group Acceptor)ZFYVE1 protein, humanATG14ATG14–BATS domainautophagyPIPKIγi5PtdIns(4,5)P2

Identifiers

PMID27621469
PMCPMC5047215
OpenAlexW2519374110

What OpenQuestion holds

Textmetadata
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.