Evidence map›Paper›PMID 31642061›Full record

ArticleFEBS letters2020

Cancer-associated mutations in human pyruvate kinase M2 impair enzyme activity.

Vivian M Liu, Andrea J Howell, Aaron M Hosios, Zhaoqi Li, William J Israelsen, Matthew G Vander Heiden

Open access · bronzeAbstract read
In one paragraph

Article in FEBS letters, 2020. 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
0.9field-weighted citation impact, top 30% 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, 25 citations in OpenAlex.

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  10. Targeting Energy Metabolism in Cancer Treatment.International journal of molecular sciences · 2022
    Review
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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 3 institutions in 1 country.

Vivian M LiuDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Andrea J HowellDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Aaron M HosiosDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Zhaoqi LiDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
William J IsraelsenDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0002-3653-9353
Matthew G Vander HeidenDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0002-6702-4192
Massachusetts Institute of Technology · USDana-Farber Cancer Institute · USHarvard University · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Kristin A Knouse · 1985 to 2026
$93.9M
PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8M
Understanding the role of metabolism in cancerR35CA242379 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI VANDER HEIDEN, MATTHEW G. · 2019 to 2025
$5.8M
Development and use of a novel, tractable rodent model for studies of hibernation metabolismDP5OD021365 · OD · UT SOUTHWESTERN MEDICAL CENTER · PI ISRAELSEN, WILLIAM JAMES · 2015 to 2019
$1.9M
Regulation of glucose metabolism to allow tumor initiation and growthR01CA168653 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI VANDER HEIDEN, MATTHEW G. · 2013 to 2019
$1.9M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA014051NCI NIH HHS R01 CA168653NCI NIH HHS R35 CA242379NIGMS NIH HHS T32 GM007287NIH HHS DP5 OD021365NIH HHS P30CA1405141
6 · The paper itself

Abstract

Mammalian pyruvate kinase catalyzes the final step of glycolysis, and its M2 isoform (PKM2) is widely expressed in proliferative tissues. Mutations in PKM2 are found in some human cancers; however, the effects of these mutations on enzyme activity and regulation are unknown. Here, we characterized five cancer-associated PKM2 mutations, occurring at various locations on the enzyme, with respect to substrate kinetics and activation by the allosteric activator fructose-1,6-bisphosphate (FBP). The mutants exhibit reduced maximal velocity, reduced substrate affinity, and/or altered activation by FBP. The kinetic parameters of five additional PKM2 mutants that have been used to study enzyme function or regulation also demonstrate the deleterious effects of mutations on PKM2 function. Our findings indicate that PKM2 is sensitive to many amino acid changes and support the hypothesis that decreased PKM2 activity is selected for in rapidly proliferating cells.

Indexed as

MutationCarrier ProteinsHumansKineticsMembrane ProteinsNeoplasmsProtein MultimerizationProtein Structure, QuaternaryThyroid Hormone-Binding ProteinsThyroid HormonesCarrier ProteinsMembrane ProteinsThyroid Hormone-Binding ProteinsThyroid Hormonesallosterycancerenzymologymutation

Identifiers

PMID31642061
PMCPMC7042059
OpenAlexW2981375846

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.