Evidence map›Paper›PMID 39392755›Full record

ArticleCell reports2024

ERK1/2 interaction with DHPS regulates eIF5A deoxyhypusination independently of ERK kinase activity.

Andrew E Becker, Paweł Kochanowski, Pui-Kei Wu, Elżbieta Wątor, Wenjing Chen, Koushik Guchhait, Artur P Biela, Przemysław Grudnik, Jong-In Park

Abstract read
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

9 authors.

Andrew E BeckerDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Paweł KochanowskiDoctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, Poland; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
Pui-Kei WuDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Elżbieta WątorDoctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, Poland; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
Wenjing ChenDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Koushik GuchhaitDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Artur P BielaMalopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
Przemysław GrudnikMalopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland. Electronic address: przemyslaw.grudnik@uj.edu.pl.
Jong-In ParkDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: jipark@mcw.edu.

Funding

Mechanisms of MEK/ERK growth arrest signalingR01CA138441 · NCI · MEDICAL COLLEGE OF WISCONSIN · PI PARK, JONG-IN · 2010 to 2020
$2.9M
The Role of Mortalin in Thyroid CancerR01CA269452 · NCI · MEDICAL COLLEGE OF WISCONSIN · PI Jong-In Park · 2023 to 2026
$1.7M
NCI NIH HHS R01 CA138441NCI NIH HHS R01 CA269452
6 · The paper itself

Abstract

This study explores a non-kinase effect of extracellular regulated kinases 1/2 (ERK1/2) on the interaction between deoxyhypusine synthase (DHPS) and its substrate, eukaryotic translation initiation factor 5A (eIF5A). We report that Raf/MEK/ERK activation decreases the DHPS-ERK1/2 interaction while increasing DHPS-eIF5A association in cells. We determined the cryoelectron microscopy (cryo-EM) structure of the DHPS-ERK2 complex at 3.5 Å to show that ERK2 hinders substrate entrance to the DHPS active site, subsequently inhibiting deoxyhypusination in vitro. In cells, impairing the ERK2 activation loop, but not the catalytic site, prolongs the DHPS-ERK2 interaction irrespective of Raf/MEK signaling. The ERK2 Ser-Pro-Ser motif, but not the common docking or F-site recognition sites, also regulates this complex. These data suggest that ERK1/2 dynamically regulate the DHPS-eIF5A interaction in response to Raf/MEK activity, regardless of its kinase function. In contrast, ERK1/2 kinase activity is necessary to regulate the expression of DHPS and eIF5A. These findings highlight an ERK1/2-mediated dual kinase-dependent and -independent regulation of deoxyhypusination.

Indexed as

Eukaryotic Translation Initiation Factor 5APeptide Initiation FactorsRNA-Binding ProteinsCryoelectron MicroscopyHEK293 CellsHumansMAP Kinase Signaling SystemMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Oxidoreductases Acting on CH-NH Group DonorsProtein Bindingdeoxyhypusine synthaseEukaryotic Translation Initiation Factor 5AMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Oxidoreductases Acting on CH-NH Group DonorsPeptide Initiation FactorsRNA-Binding ProteinsCP: Molecular biologycryo-EMcryogenic electron microscopydeoxyhypusine synthaseeukaryotic translation initiation factor 5Aextracellular-signal-regulated kinase 1/2hypusinationhypusineMAP kinasenon-kinase effectRaf/MEK/ERK pathway

Identifiers

PMID39392755
PMCPMC11544350

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.