RGD Reference Report - Metabolic cooperation between different oncogenes during cell transformation: interaction between activated ras and HPV-16 E7. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Metabolic cooperation between different oncogenes during cell transformation: interaction between activated ras and HPV-16 E7.

Authors: Mazurek, S  Zwerschke, W  Jansen-Dürr, P  Eigenbrodt, E 
Citation: Mazurek S, etal., Oncogene. 2001 Oct 18;20(47):6891-8. doi: 10.1038/sj.onc.1204792.
RGD ID: 152176659
Pubmed: PMID:11687968   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.onc.1204792   (Journal Full-text)

The metabolism of tumor cells (tumor metabolome) is characterized by a high concentration of glycolytic enzymes including pyruvate kinase isoenzyme type M2 (M2-PK), a high glutaminolytic capacity, high fructose 1,6-bisphosphate (FBP) levels and a low (ATP+GTP):(CTP+UTP) ratio. The sequence of events required for the establishment of the tumor metabolome is presently unknown. In non-transformed rat kidney (NRK) cells we observed a high glutaminolytic flux rate and a low (ATP+GTP):(CTP+UTP) ratio, whereas FBP levels and M2-PK activity are still extremely low. After stable expression of oncogenic ras in NRK cells a strong upregulation of FBP levels and of M2-PK activity was observed. Elevated FBP levels induce a tetramerization of M2-PK and its migration into the glycolytic enzyme complex. AMP levels increase whereas UTP and CTP levels strongly decrease. Thus, ras expression completes the glycolytic part of tumor metabolism leading to the inhibition of nucleic acid synthesis and cell proliferation. The HPV-16 E7 oncoprotein, which cooperates with ras in cell transformation, directly binds to M2-PK, induces its dimerization and restores nucleic acid synthesis as well as cell proliferation. Apparently, the combination of the different metabolic effects of ras and E7 constructs the perfect tumor metabolome as generally found in tumor cells.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PkmRatprotein tetramerization  IDA  RGD 

Molecular Function
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PkmRatprotein dimerization activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pkm  (pyruvate kinase M1/2)


Additional Information