Evidence map›Paper›PMID 38467653›Full record

ArticleNature communications2024

Simultaneous proteome localization and turnover analysis reveals spatiotemporal features of protein homeostasis disruptions.

Jordan Currie, Vyshnavi Manda, Sean K Robinson, Celine Lai, Vertica Agnihotri, Veronica Hidalgo, R W Ludwig, Kai Zhang, Jay Pavelka, Zhao V Wang and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
5.3field-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

17 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Review
  3. Subcellular localization as a driver of protein function.Nature reviews. Molecular cell biology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Jordan CurrieDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Vyshnavi MandaDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Sean K RobinsonDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA.ORCID 0009-0008-4761-3871
Celine LaiStanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA.
Vertica AgnihotriDepartment of Medicine, Division of Cardiology, City of Hope Comprehensive Cancer Center, CA, 91010, Duarte, USA.
Veronica HidalgoDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
R W LudwigDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Kai ZhangDepartment of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, 91010, USA.ORCID 0009-0009-7164-9556
Jay PavelkaDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Zhao V WangDepartment of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, 91010, USA.ORCID 0000-0002-9904-9538
June-Wha RheeDepartment of Medicine, Division of Cardiology, City of Hope Comprehensive Cancer Center, CA, 91010, Duarte, USA.
Maggie P Y LamDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA.ORCID 0000-0001-9488-8319
Edward LauDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA. edward.lau@cuanschutz.edu.ORCID 0000-0001-9083-5922
University of Colorado Denver · USCity of Hope · USCity Of Hope National Medical Center · USCardiovascular Institute of the South · US

Funding

Alternative Protein Isoforms in Ventricular RemodelingR01HL141278 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI Maggie Lam · 2018 to 2026
$3.5M
Post-transcriptional regulations of proteomes in stress and senescenceR01GM144456 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI LAM, MAGGIE · 2022 to 2025
$2.2M
Investigations of Proteome Turnover Kinetics Under Cellular DifferentiationR35GM146815 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI Edward Lau · 2022 to 2026
$2.1M
Patient-specific modeling of metabolic dysfunction in statin-induced myopathy using iPSC-derived myocytesK08HL148540 · NHLBI · STANFORD UNIVERSITY · PI RHEE, JUNE-WHA · 2020 to 2024
$760k
NHLBI NIH HHS K08 HL148540NHLBI NIH HHS R01 HL141278NIGMS NIH HHS R01 GM144456NIGMS NIH HHS R35 GM146815
6 · The paper itself

Abstract

The spatial and temporal distributions of proteins are critical to protein function, but cannot be directly assessed by measuring protein bundance. Here we describe a mass spectrometry-based proteomics strategy, Simultaneous Proteome Localization and Turnover (SPLAT), to measure concurrently protein turnover rates and subcellular localization in the same experiment. Applying the method, we find that unfolded protein response (UPR) has different effects on protein turnover dependent on their subcellular location in human AC16 cells, with proteome-wide slowdown but acceleration among stress response proteins in the ER and Golgi. In parallel, UPR triggers broad differential localization of proteins including RNA-binding proteins and amino acid transporters. Moreover, we observe newly synthesized proteins including EGFR that show a differential localization under stress than the existing protein pools, reminiscent of protein trafficking disruptions. We next applied SPLAT to an induced pluripotent stem cell derived cardiomyocyte (iPSC-CM) model of cancer drug cardiotoxicity upon treatment with the proteasome inhibitor carfilzomib. Paradoxically, carfilzomib has little effect on global average protein half-life, but may instead selectively disrupt sarcomere protein homeostasis. This study provides a view into the interactions of protein spatial and temporal dynamics and demonstrates a method to examine protein homeostasis regulations in stress and drug response.

Indexed as

ProteomeProteostasisGolgi ApparatusHumansMass SpectrometryUnfolded Protein ResponseProteome

Identifiers

PMID38467653
PMCPMC10928085
OpenAlexW4392638185

What OpenQuestion holds

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LicenceCC BY
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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.