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- Co-ordination of G1 Progression
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1. START control in yeast
- Prof. Curt Wittenberg
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2. The pRB/E2F pathway
- Prof. Jacqueline Lees
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3. Cell cycle control by the ubiquitin system in mammals
- Prof. Michele Pagano
- Chromosome Duplication
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4. Replication licensing
- Prof. Julian Blow
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5. Initiation of DNA replication
- Prof. Bruce Stillman
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6. Regulation of replication fork progression and stability
- Dr. Luis Aragón
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7. Nucleosome assembly during DNA replication
- Dr. Alain Verreault
- Preparing for Mitosis
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8. Sister chromatid cohesion: simple concept, complex reality
- Prof. Douglas Koshland
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9. Mitotic chromosome condensation
- Prof. Andrew Belmont
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10. Centrosome duplication and separation in animal cells
- Prof. Andrew Fry
- Spindle Assembly and Chromosome Segregation
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11. Bipolar spindle assembly
- Dr. Eric Karsenti
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12. Chromosome bi-orientation in yeast
- Prof. Mike Stark
- Prof. Tomo Tanaka
- Mitotic Exit and Cytokinesis
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14. Cleavage furrow formation and ingression during animal cytokinesis
- Dr. Pier Paolo D'Avino
- Checkpoints Governing Cell Cycle Progression
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15. The DNA damage response
- Dr. Vincenzo Costanzo
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16. The spindle checkpoint
- Dr. Kevin Hardwick
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17. Spindle movement and checkpoint control during mitosis in yeast
- Prof. John Cooper
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18. The G2/M transition
- Prof. Dr. René Medema
- The Cell Cycle in Development and Cancer
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19. Mouse models to investigate cell cycle and cancer
- Dr. Philipp Kaldis
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20. Cell cycle: a complex network of signals regulating cell proliferation
- Prof. Antonio Giordano
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21. Drug discovery and target validation in the p53 pathway
- Prof. Sir David Lane
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22. Role and regulation of Cdk inhibitors in development and cancer
- Prof. Martine Roussel
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24. The Myc transcription factor network
- Prof. Robert N. Eisenman
- Meiosis: A Specialized Cell Cycle
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25. Recombination and the formation of chiasmata in meiosis
- Prof. Matthew Whitby
- Archived Lectures *These may not cover the latest advances in the field
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26. Geometric regulation of kinetochore orientation
- Prof. Yoshinori Watanabe
Printable Handouts
Navigable Slide Index
- Introduction
- Controlling cancer
- Talk outline
- 1978: discovery of p53
- 1979: p53 first published results
- Co-immunoprecipitation of T-antigen and p53
- DNA virus proteins inactivate p53 and Rb: SV40
- DNA virus proteins inactivate p53 and Rb: Adeno
- DNA virus proteins inactivate p53 and Rb: HPV
- Schematic representation of the p53 protein
- Anti-p53 Abs stain in nuclei of human cancer cells
- Incidence of p53 mutations in human cancers
- Crystal structure of the p53 DNA-binding region
- What does p53 do?
- The p53 pathway is blocked in many tumour cells
- Negative feedback loop of p53 and HDM2
- Mdm2 controls p53 - genetic experiments
- Evidence for the fine regulation of the p53 response
- How does p53 cause advanced aging?
- Therapy approaches
- Approval of gene therapy in China - not the U.S.
- Activating p53
- Blockage of p53/HDM interaction activates p53
- Peptide minimisation and optimisation
- Induction of p53 by peptide 7 epimer F2
- Binding of bisarylsulfonamides to HDM2
- Nutlin: inhibitor of the p53-MDM2 interaction
- Nutlin 3 specificity
- Testing compounds for their ability to activate p53
- Summary of screening 35,000 compounds
- CYC202: a cdk inhibitor in clinical trials
- Tumour suppressors induce small CDK inhibitors
- CDK inhibition
- Specificity of CYC202 in vitro
- CYC202 effect on tumour growth
- Biomarkers for CYC202 p53 induction
- Inhibition of transcription can trigger apoptosis
- Hypothesis: activation of p53 by CYC202
- Stress stimuli that control the activity of p53
- New isoforms of p53
- Jean Christophe Bourdon
- Putative p53 protein isoforms
- Acknowledgments (1)
- Acknowledgments (2)
Topics Covered
- Controlling cancer
- p53 discovery
- Oncoproteins
- SV40, Adeno and HPV
- The p53 protein
- Incidence of genetic changes in p53 in human cancers
- What does p53 do?
- The p53 pathway is blocked in many tumor cells
- p53 and HDM2 are connected by a negative feedback loop
- Mdm2 controls p53
- Evidence for the fine regulation of the p53 response
- How does p53 cause advanced aging?
- Therapy approaches
- Gene therapy
- Activating p53
- Targets for p53 activation
- Small peptides block p53/HDM interaction and activate p53
- Peptide minimization and optimization
- Nutlin 3 specificity
- Thousands of compounds can be tested for their ability to activate p53-dependent transcription
- CYC202: a cdk inhibitor in clinical trial that is a non genotoxic activator of the p53 response
- CDK inhibition
- Regulation of p53 by ubiquitin like proteins
- Stress stimuli that control the activity of p53
- New isoforms of p53
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Lane, D. (2009, June 28). Drug discovery and target validation in the p53 pathway [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved April 19, 2025, from https://doi.org/10.69645/FIXN5797.Export Citation (RIS)
Publication History
- Published on June 28, 2009
Financial Disclosures
- Prof. Sir David Lane has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Drug discovery and target validation in the p53 pathway
Published on June 28, 2009
40 min