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Presentation For Capstone Project
ForThe partial fulfillment of B.Tech
(Biotech.) Hons.
Dec20, 2010
Topic: Metabolic role of humanp53 in cancer
By:
Rahul ThakurRoll Number A77E401
Section A77E4
Guide : Dr. Abhay Kumar
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Objective.
The objective of the current work was to collectthe information from the related and recent
articles and present some logical conclusionsout of it.
-and to focus mainly on the role of p53 in cancermetabolism
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Role of
p53
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Recent researches suggests that p53, the
most commonly mutated tumor suppressor
gene, might play an important role in theregulation of energy generating metabolic
pathways, that switch from oxidative
phosphorylation to glycolysis
p53
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generation of ATP through oxidative phosphorylation isan efficient and preferred metabolic process,
which produces far more ATP molecules from a given
amount of glucose compared with glycolysis.However, when the ability of cells to generate ATPthrough mitochondrial oxidative phosphorylation iscompromised, cells are able to adapt alternativemetabolic pathways, such as increasing glycolyticactivity, to maintain their energy supply.
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As per Warburg when the
cell is present in thenormal state i.e., in normalOxygen level it follows the
Krebs's cycle pathway, but
under the stress conditionswhen the oxygen levelbecomes low the cancercells automatically shifttheir metabolism to the
glycolysis
http://TheNaturalCancerCure.com
Review Of Literature
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Objections
Since according to the Warburg cancercell follow the glycolysis when O2 level islow ..but many researchers found thateven in the adequate amount of the O2cancer cell still follow glycolysis
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possible Target ???
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pyruvate kinase has emerged as a keyplayer in maintaining the altered
metabolism of cancer cells and is thus apotential target for cancer drugs.
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Glycolysis Pathway
Target
Protein Kinase-M2
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Protein Kinase exists in two
formsdimeric form and tetrameric form
which shows a high affinity for the substrate
phosphoenolpyruvate (PEP), and the dimeric form,which has a low affinity for PEP. The dimeric form
predominates in tumours and was thereforenamed Tumor M2-PK
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Tumour cells have been shown to
express exclusively the embryonic M2isoform of pyruvate kinase.
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Either Supress this glycolysis pathway
Block the target enzymeseg.fructose
1-6 biphosphate Make the PMK1 active
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Conclusion
After this elaborate study we can conclude
that there are certain pathways involved incancer which can be regulated at specificstages before onset of cancer that can betargeted to design drugs which can beeffective against preventing cancer
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ReferencesVausden .et al.( 2006 ) p53: new roles in metabolism TRENDS in Cell Biology
Vol.17 No.6
Sabatini Hsu .et al. (2004) Cancer Cell Metabolism:Warburg and Beyond cell biology
Heather R. Christofk1, Matthew G. Vander Heiden1,3, Ning Wu1, John M. Asara2,4
& Lewis C. Cantley1,4
Christofk, H. R.; Vander Heiden, M. G.; Harris, M. H.;Ramanathan, A.; Gerszten, R. E.; Wei, R.; Fleming, M. D.; Schreiber, S. L.; Cantley,L. C.: The M2 splice isoform of pyruvate kinase is important for cancer metabolismand tumour growth. Nature 452: 230-233, 2008.
9. Matoba,
Matoba, S. et al. (2006) p53 regulates mitochondrial respiration.Science 312, 16501653
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Thank you