Evidence map›Paper›PMID 25128814›Full record

ArticleExperimental cell research2014

Raf/MEK/ERK can regulate cellular levels of LC3B and SQSTM1/p62 at expression levels.

Jin-Hwan Kim, Seung-Keun Hong, Pui-Kei Wu, Alexsia L Richards, William T Jackson, Jong-In Park

Open access · greenAbstract read
In one paragraph

Article in Experimental cell research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 2 pooled it
6.0field-weighted citation impact, top 3% 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

60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 116 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Jin-Hwan KimDepartment of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Seung-Keun HongDepartment of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Pui-Kei WuDepartment of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Alexsia L RichardsDepartment of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
William T JacksonDepartment of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Jong-In ParkDepartment of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: jipark@mcw.edu.
Medical College of Wisconsin · US

Funding

Mechanisms of MEK/ERK growth arrest signalingR01CA138441 · NCI · MEDICAL COLLEGE OF WISCONSIN · PI PARK, JONG-IN · 2010 to 2020
$2.9M
NCI NIH HHS R01 CA138441NCI NIH HHS R01CA138441
6 · The paper itself

Abstract

While cellular LC3B and SQSTM1 levels serve as key autophagy markers, their regulation by different signaling pathways requires better understanding. Here, we report the mechanisms by which the Raf/MEK/ERK pathway regulates cellular LC3B and SQSTM1 levels. In different cell types, ΔRaf-1:ER- or B-Raf(V600E)-mediated MEK/ERK activation increased LC3B-I, LC3B-II, and SQSTM1/p62 levels, which was accompanied by increased BiP/GRP78 expression. Use of the autophagy inhibitors chloroquine and bafilomycin A1, or RNA interference of ATG7, suggested that these increases in LC3B and SQSTM1 levels were in part attributed to altered autophagic flux. However, intriguingly, these increases were also attributed to their increased expression. Upon Raf/MEK/ERK activation, mRNA levels of LC3B and SQSTM1 were also increased, and subsequent luciferase reporter analyses suggested that SQSTM1 upregulation was mediated at transcription level. Under this condition, transcription of BiP/GRP78 was also increased, which was necessary for Raf/MEK/ERK to regulate LC3B at the protein, but not mRNA, level. This suggests that BiP has a role in regulating autophagy machinery when Raf/MEK/ERK is activated. In conclusion, these results suggest that, under a Raf/MEK/ERK-activated condition, the steady-state cellular levels of LC3B and SQSTM1 can also be determined by their altered expression wherein BiP is utilized as an effector of the signaling.

Indexed as

Adaptor Proteins, Signal TransducingApoptosisAutophagyBlotting, WesternCell ProliferationCells, CulturedEndoplasmic Reticulum Chaperone BiPFibroblastsGene Expression Regulation, NeoplasticHeat-Shock ProteinsHumansMaleMAP Kinase Kinase 1Microtubule-Associated ProteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Adaptor Proteins, Signal TransducingEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsHSPA5 protein, humanMAP1LC3B protein, humanMAP2K1 protein, humanMAPK1 protein, humanMAP Kinase Kinase 1Microtubule-Associated ProteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3raf KinasesRNA, MessengerSequestosome-1 ProteinSQSTM1 protein, humanAutophagyBiP/GRP78ERK1/2LC3RafSQSTM1

Identifiers

PMID25128814
PMCPMC4164593
OpenAlexW2080390339

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.