Evidence map›Paper›PMID 40273915›Full record

ArticleMolecular cell2025

Pooled tagging and hydrophobic targeting of endogenous proteins for unbiased mapping of unfolded protein responses.

Stephanie E Sansbury, Yevgeniy V Serebrenik, Tomer Lapidot, David G Smith, George M Burslem, Ophir Shalem

Abstract read
In one paragraph

Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

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  7. Designing the Proteome with Chemical Tools: Degrons and Beyond.Chembiochem : a European journal of chemical biology · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Stephanie E SansburyCenter for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yevgeniy V SerebrenikCenter for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: yevgeniy.serebrenik@rutgers.edu.
Tomer LapidotCenter for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
David G SmithCenter for Single Cell Biology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
George M BurslemDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ophir ShalemCenter for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: shalemo@upenn.edu.

Funding

PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM008216 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, DOUGLAS J · 1987 to 2023
$8.3M
Direct and rapid control of proteins at scaleDP2GM137416 · NIGMS · CHILDREN'S HOSP OF PHILADELPHIA · PI SHALEM, OPHIR · 2019 to 2022
$2.8M
Editing Acetylation and Protein HomeostasisR35GM142505 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI George Burslem · 2021 to 2026
$2.7M
Uncovering cell factors with aggregate clearance activity by scalable induced proximityR00AG075256 · NIA · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI Yevgeniy Vladimirovich Serebrenik · 2025 to 2026
$498k
Dissecting the mechanisms that underlie mislocalization and aggregation of RNA binding proteins in neurodegenerative diseasesR03NS111447 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI SHALEM, OPHIR · 2019 to 2019
$352k
Uncovering cell factors with aggregate clearance activity by scalable induced proximityK99AG075256 · NIA · CHILDREN'S HOSP OF PHILADELPHIA · PI SEREBRENIK, YEVGENIY VLADIMIROVICH · 2022 to 2023
$259k
Rapid and direct control of the proteome through a multiplexed tag systemF32CA239499 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI SEREBRENIK, YEVGENIY VLADIMIROVICH · 2019 to 2021
$195k
Coupling a multifunctional tag to scalable endogenous tagging technology for improved genome-wide perturbation screensF31HG011185 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI SANSBURY, STEPHANIE ELIZABETH · 2020 to 2022
$113k
NCI NIH HHS F32 CA239499NHGRI NIH HHS F31 HG011185NIA NIH HHS K99 AG075256NIA NIH HHS R00 AG075256NIGMS NIH HHS DP2 GM137416NIGMS NIH HHS R35 GM142505NIGMS NIH HHS T32 GM008216NINDS NIH HHS R03 NS111447
6 · The paper itself

Abstract

To achieve system-level insights into proteome organization, regulation, and function, we developed an approach to generate complex cell pools with endogenously tagged proteins amenable to high-throughput visualization and perturbation. Pooled imaging coupled to in situ barcode sequencing identified the subcellular localization of each HaloTag-tagged protein, and subsequent ligand-induced misfolding of the library followed by single-cell RNA sequencing revealed responses to spatially restricted protein misfolding. These datasets characterized protein quality control responses in previously uninterrogated cellular compartments, and cross-compartment analyses revealed mutually exclusive rather than collaborative responses, whereby the heat shock response (HSR) is induced in some compartments and repressed in others where autophagy genes are induced. We further assign protein quality control functions to previously uncharacterized genes based on shared transcriptional responses to protein misfolding across cellular compartments. Altogether, we present an efficient method for large-scale studies of proteome dynamics, function, and homeostasis.

Indexed as

ProteomeProteomicsUnfolded Protein ResponseAutophagyHeat-Shock ResponseHEK293 CellsHeLa CellsHumansHydrophobic and Hydrophilic InteractionsProtein FoldingProteostasisSingle-Cell AnalysisProteomehydrophobic targetingin situ sequencingpooled taggingprotein localizationprotein misfoldingproteostasis

Identifiers

PMID40273915
PMCPMC12115883

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Registered trials

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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.