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E2F

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Transcript

  • 1.  
  • 2. pRB Binds to the E2F Transcription Factor
  • 3. Figure 8.23c The Biology of Cancer (© Garland Science 2007)
  • 4. Figure 8.23b The Biology of Cancer (© Garland Science 2007)
  • 5.  
  • 6. G1 Cyclin CDKs Phosphorylate pRB
  • 7. Sites of RB Missense Mutations in Tumors A B The A and B domain = pocket = where E2F binds
  • 8. Tumorigenesis in RB Mutant Mice Requires E2F Yamasaki et al, Nat. Gen. 18:360 (1998) 0/22 (0%) 16/26 (62%) RB (+/-); E2F1 (-/-) 2/34 (6%) 36/36 (100%) RB (+/-); E2F1 (+/-) 10/19 (53%) 19/20 (95%) RB (+/-) Thyroid Tumors Pituitary Tumors Genotype
  • 9. Proliferation Signals p16 Regulates pRB Phosphorylation
  • 10. p16 is a Human Tumor Suppressor Data Courtesy of Dr. Ned Sharpless These estimates are derived only from analyses of primary tumors, and exclude cell line data. 299.9 0.31 972.4 Total 31.7 0.20 158.5 Other 6.1 0.60 10.1 Multiple Myeloma 7.7 0.70 11.0 Esophagus 0.4 0.03 13.5 Thyroid 7.1 0.44 16.1 Stomach 4.1 0.25 16.2 Ovary 18.6 0.85 21.9 Pancreas 14.2 0.61 23.3 Leukemias 4.3 0.18 23.9 Endometrium 1.2 0.05 24.4 Kidney 20.2 0.65 31.1 Melanoma 21.6 0.68 31.7 Head and Neck 1.1 0.03 35.7 Lung, Small cell 12.4 0.33 37.7 Lymphoma, non-Hodgkin's 28.5 0.59 48.3 Bladder 17.9 0.27 66.4 Colorectal 68.2 0.64 106.6 Lung, Non-small cell 28.1 0.21 134.0 Breast 6.5 0.04 162.0 Prostate Total Cases p16 Loss Freq. p16 Loss Annual Incidence Tumor Type
  • 11. Proliferation Signals The Canonical p16/pRB/E2F “ Pathway”
  • 12. Sherr and McCormick, Cancer Cell ·2:103 (2002) The RB Pathway in Human Cancer (p16)
  • 13.