ArticleThe Journal of biological chemistry2010
Dominant negative mutations affect oligomerization of human pyruvate kinase M2 isozyme and promote cellular growth and polyploidy.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Homogentisate 1,2-dioxygenase (HGD) gene variants, their analysis and genotype-phenotype correlations in the largest cohort of patients with AKU.European journal of human genetics : EJHG · 2019Trial
- Alkaptonuria.Nature reviews. Disease primers · 2024Review
- HPV18 oncoproteins driven expression of PKM2 reprograms HeLa cell metabolism to maintain aerobic glycolysis and viability.Virusdisease · 2022Article
- Article
- Alkaptonuria: Current Perspectives.The application of clinical genetics · 2020Review
- PKM2, function and expression and regulation.Cell & bioscience · 2019Review
- Pyruvate kinase M knockdown-induced signaling via AMP-activated protein kinase promotes mitochondrial biogenesis, autophagy, and cancer cell survival.The Journal of biological chemistry · 2017Article
- Deubiquitinases and cancer: A snapshot.Critical reviews in oncology/hematology · 2016Review
- ERK2-Pyruvate Kinase Axis Permits Phorbol 12-Myristate 13-Acetate-induced Megakaryocyte Differentiation in K562 Cells.The Journal of biological chemistry · 2015Article
- Moderate DNA damage promotes metabolic flux into PPP via PKM2 Y-105 phosphorylation: a feature that favours cancer cells.Molecular biology reports · 2015Article
- Pyruvate kinase M2 at a glance.Journal of cell science · 2015Review
- Structural insight into mechanisms for dynamic regulation of PKM2.Protein & cell · 2015Article
- In silico screening, genotyping, molecular dynamics simulation and activity studies of SNPs in pyruvate kinase M2.PloS one · 2015Article
- Molecular simulation of Tyr105 phosphorylated pyruvate kinase M2 to understand its structure and dynamics.Journal of molecular modeling · 2014Article
- Missense mutations in pyruvate kinase M2 promote cancer metabolism, oxidative endurance, anchorage independence, and tumor growth in a dominant negative manner.The Journal of biological chemistry · 2014Article
- Insulin enhances metabolic capacities of cancer cells by dual regulation of glycolytic enzyme pyruvate kinase M2.Molecular cancer · 2013Article
- Resveratrol inhibits cancer cell metabolism by down regulating pyruvate kinase M2 via inhibition of mammalian target of rapamycin.PloS one · 2012Article
- Human pyruvate kinase M2: a multifunctional protein.Protein science : a publication of the Protein Society · 2010Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study was designed to understand the mechanism and functional implication of the two heterozygous mutations (H391Y and K422R) of human pyruvate kinase M2 isozyme (PKM(2)) observed earlier in a Bloom syndrome background. The co-expression of homotetrameric wild type and mutant PKM(2) in the cellular milieu resulting in the interaction between the two at the monomer level was substantiated further by in vitro experiments. The cross-monomer interaction significantly altered the oligomeric state of PKM(2) by favoring dimerization and heterotetramerization. In silico study provided an added support in showing that hetero-oligomerization was energetically favorable. The hetero-oligomeric populations of PKM(2) showed altered activity and affinity, and their expression resulted in an increased growth rate of Escherichia coli as well as mammalian cells, along with an increased rate of polyploidy. These features are known to be essential to tumor progression. This study provides insight in understanding the modulated role of large oligomeric multifunctional proteins such as PKM(2) by affecting cellular behavior, which is an essential observation to understand tumor sustenance and progression and to design therapeutic intervention in future.
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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.