Evidence map›Paper›PMID 31181072›Full record

ArticlePLoS biology2019

Phenotypic selection with an intrabody library reveals an anti-apoptotic function of PKM2 requiring Mitofusin-1.

Tong Liu, Tomomi Kuwana, Hongkai Zhang, Matthew G Vander Heiden, Richard A Lerner, Donald D Newmeyer

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 35% 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

10 citing papers in PubMed, 17 citations in OpenAlex.

  1. Technologies for Monoclonal Antibody Discovery and Development.International journal of molecular sciences · 2025
    Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Applying Antibodies Inside Cells: Principles and Recent Advances in Neurobiology, Virology and Oncology.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020
    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

6 authors at 3 institutions in 1 country.

Tong LiuLa Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
Tomomi KuwanaLa Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
Hongkai ZhangDepartment of Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Matthew G Vander HeidenDavid H. Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Richard A LernerDepartment of Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Donald D NewmeyerLa Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.ORCID 0000-0003-1736-2780
La Jolla Institute for Immunology · USScripps Research Institute · USMassachusetts Institute of Technology · US

Funding

MITOCHONDRIAL FUNCTION IN APOPTOSISR01GM062289 · NIGMS · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI NEWMEYER, DONALD DAVID · 2001 to 2013
$4.3M
Molecular mechanism of BCL2-dependent apoptosisR01CA179087 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI HANEIN, DORIT, MARASSI, FRANCESCA M · 2014 to 2018
$3.6M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA179087NIGMS NIH HHS R01 GM062289
6 · The paper itself

Abstract

Bcl-2 family proteins control a decisive apoptotic event: mitochondrial outer membrane permeabilization (MOMP). To discover MOMP-regulating proteins, we expressed a library of intracellular single-chain variable fragments (scFvs) ("intrabodies") and selected for those rescuing cells from apoptosis induced by BimS (the short isoform of Bim). One anti-apoptotic intrabody, intrabody 5 (IB5), recognized pyruvate kinase M2 (PKM2), which is expressed in cancer cells. PKM2 deletion ablated this clonogenic rescue; thus, IB5 activated a latent cytoprotective function of PKM2. This resulted not from pyruvate kinase activity per se but rather from the formation of an active tetrameric conformation of PKM2. A stably tetrameric PKM2 mutant, K422R, promoted cell survival even in the absence of IB5, and IB5 further increased survival. Mitochondria isolated from IB5-expressing cells were relatively resistant to MOMP in vitro. In cells, IB5 expression up-regulated Mitofusin-1 (Mfn1) and increased mitochondrial length. Importantly, Mfn1 deficiency abrogated IB5's cytoprotective effect. PKM2's anti-apoptotic function could help explain its preferential expression in human cancer.

Indexed as

Amino Acid SequenceApoptosisBcl-2-Like Protein 11Carrier ProteinsCell Line, TumorCell Membrane PermeabilityCell ProliferationGene LibraryGTP PhosphohydrolasesHEK293 CellsHumansMembrane ProteinsMitochondriaMitochondrial MembranesMitochondrial Membrane Transport ProteinsProtein IsoformsBcl-2-Like Protein 11Carrier ProteinsGTP PhosphohydrolasesMembrane ProteinsMfn1 protein, humanMitochondrial Membrane Transport ProteinsProtein IsoformsPyruvate KinaseSingle-Chain Antibodies

Identifiers

PMID31181072
PMCPMC6586363
OpenAlexW2952300279

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.