Evidence map›Paper›PMID 29313410›Full record

ArticleAutophagy2018

ULK1 phosphorylates Ser30 of BECN1 in association with ATG14 to stimulate autophagy induction.

Ji-Man Park, Minchul Seo, Chang Hwa Jung, Douglas Grunwald, Matthew Stone, Neil Michael Otto, Erik Toso, Yeseul Ahn, Michael Kyba, Timothy J Griffin and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 1 pooled it
11.3field-weighted citation impact, top 1% 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

106 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.

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  8. The human autophagy-initiating complexes ULK1C and PI3KC3-C1.The Journal of biological chemistry · 2025
    Review
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46 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

12 authors at 1 institution in 2 countries.

Ji-Man Parka Department of Biochemistry , Molecular Biology, and Biophysics , University of Minnesota , Minneapolis, MN , USA.
Minchul Seoa Department of Biochemistry , Molecular Biology, and Biophysics , University of Minnesota , Minneapolis, MN , USA.
Chang Hwa Junga Department of Biochemistry , Molecular Biology, and Biophysics , University of Minnesota , Minneapolis, MN , USA.
Douglas Grunwalda Department of Biochemistry , Molecular Biology, and Biophysics , University of Minnesota , Minneapolis, MN , USA.
Matthew Stonea Department of Biochemistry , Molecular Biology, and Biophysics , University of Minnesota , Minneapolis, MN , USA.
Neil Michael Ottoa Department of Biochemistry , Molecular Biology, and Biophysics , University of Minnesota , Minneapolis, MN , USA.
Erik Tosoc Department of Pediatrics , University of Minnesota , Minneapolis , MN , USA.
Yeseul Ahna Department of Biochemistry , Molecular Biology, and Biophysics , University of Minnesota , Minneapolis, MN , USA.
Michael Kybac Department of Pediatrics , University of Minnesota , Minneapolis , MN , USA.
Timothy J Griffina Department of Biochemistry , Molecular Biology, and Biophysics , University of Minnesota , Minneapolis, MN , USA.
LeeAnn Higginsd Center for Mass Spectrometry and Proteomics , University of Minnesota , Minneapolis , MN , USA.
Do-Hyung Kima Department of Biochemistry , Molecular Biology, and Biophysics , University of Minnesota , Minneapolis, MN , USA.ORCID 0000-0002-2924-4370
University of Minnesota · US

Funding

Obesity and Energy Metabolism CoreP30DK050456 · NIDDK · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BERNLOHR, DAVID A · 1995 to 2015
$17.0M
Probing the Activity of DUX4 in FSHDR01AR055685 · NIAMS · UNIVERSITY OF MINNESOTA · PI Michael Kyba · 2010 to 2026
$7.0M
Training Grant: Functional Proteomics of AgingT32AG029796 · NIA · UNIVERSITY OF MINNESOTA · PI EDGAR A ARRIAGA, Douglas G Mashek · 2008 to 2026
$6.6M
Mechanisms of mTOR signaling to early and late stages of autophagyR01GM097057 · NIGMS · UNIVERSITY OF MINNESOTA · PI KIM, DO-HYUNG · 2011 to 2018
$2.7M
NIAMS NIH HHS R01 AR055685NIA NIH HHS T32 AG029796NIDDK NIH HHS P30 DK050456NIGMS NIH HHS R01 GM097057
6 · The paper itself

Abstract

ULK1 (unc51-like autophagy activating kinase 1) is a serine/threonine kinase that plays a key role in regulating macroautophagy/autophagy induction in response to amino acid starvation. Despite the recent progress in understanding ULK1 functions, the molecular mechanism by which ULK1 regulates the induction of autophagy remains elusive. In this study, we determined that ULK1 phosphorylates Ser30 of BECN1 (Beclin 1) in association with ATG14 (autophagy-related 14) but not with UVRAG (UV radiation resistance associated). The Ser30 phosphorylation was induced by deprivation of amino acids or treatments with Torin 1 or rapamycin, the conditions that inhibit MTORC1 (mechanistic target of rapamycin complex 1), and requires ATG13 and RB1CC1 (RB1 inducible coiled-coil 1), proteins that interact with ULK1. Hypoxia or glutamine deprivation, which inhibit MTORC1, was also able to increase the phosphorylation in a manner dependent upon ULK1 and ULK2. Blocking the BECN1 phosphorylation by replacing Ser30 with alanine suppressed the amino acid starvation-induced activation of the ATG14-containing PIK3C3/VPS34 (phosphatidylinositol 3-kinase catalytic subunit type 3) kinase, and reduced autophagy flux and the formation of phagophores and autophagosomes. The Ser30-to-Ala mutation did not affect the ULK1-mediated phosphorylations of BECN1 Ser15 or ATG14 Ser29, indicating that the BECN1 Ser30 phosphorylation might regulate autophagy independently of those 2 sites. Taken together, these results demonstrate that BECN1 Ser30 is a ULK1 target site whose phosphorylation activates the ATG14-containing PIK3C3 complex and stimulates autophagosome formation in response to amino acid starvation, hypoxia, and MTORC1 inhibition.

Indexed as

Adaptor Proteins, Vesicular TransportAutophagyAutophagy-Related Protein-1 HomologAutophagy-Related ProteinsBeclin-1Cells, CulturedClass I Phosphatidylinositol 3-KinasesHumansIntracellular Signaling Peptides and ProteinsPhosphorylationAdaptor Proteins, Vesicular TransportATG14 protein, humanAutophagy-Related Protein-1 HomologAutophagy-Related ProteinsBeclin-1BECN1 protein, humanClass I Phosphatidylinositol 3-KinasesIntracellular Signaling Peptides and ProteinsPIK3CA protein, humanULK1 protein, humanATG14BECN1MTORC1PIK3C3ULK1

Identifiers

PMID29313410
PMCPMC5959323
OpenAlexW2782609861

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.