Functions of Onc-Gene Products: Growth Factor Receptors Signal Transduction, Nuclear Transcription Factors Folder Title: OncProteins Updated: April 20, 2010 OncProtsTitle

How Weinberg’s Biology of Cancer Book is Set Up Chapter 3: Oncogenic Viruses: There are oncogenes. Viruses Reveal Them Chapter 4: Oncogenes What these oncogenes are. How Many There Are. Where they function Chapters 5 and 6: Oncogene Products How they contribute to the neoplastic phenotype Chapter 5: Growth Factors, Growth Factor Receptors, Transmembrane Signal Transduction Chapter 6: Cytoplasmic Signal Transduction to the Nucleus Chapters 7, 8, 9: Tumor Suppressor Genes Chapter 8: Retinoblastoma Protein and Cell Cycle Control Chapter 9: p53 Tumor Suppressor Protein and Control of Apoptosis

Normal Cellular Functions for c-Onc-Gene Products (Part 1) (edited from Table 7-3, pp 288-9, Ruddon, 3rd Ed.)...Shortened Version Growth Factors sis Platelet-derived GFviral transduction int-2Fibroblast GF-relatedviral insertion Growth Factor Receptor, Tyrosine Kinase Activity erbBEpidermal GF receptor (truncated)viral transduction fmsColony-stimulating GF receptor (mutated)viral transduction neuReceptor-like (unknown ligand)DNA transfaction kitStem-cell GF receptor (truncated)viral transduction Non-receptor, Cytoplasmic Tyrosine-Kinase Activity srcMembrane-associatedviral transduction abl/bcr-ablviral transduction cOncDo1

Normal Cellular Functions for c-Onc-Gene Products (Part 2) (editted from Table 7-3, pp 288-9, Ruddon, 3rd Ed.) Cytoplasmic Serine-Kinase Activity raf/milviral transduction mos viral transduction Membrane Associated G Proteins H-ras &GTP-binding GTPasesviral transduction & DNA K-rastransfection N-rasGTP-binding GTPaseDNA Transfection Unclassified Cytoplasmic Proteins bcl-2 Anti-apoptotic* Chromosome translocations *Antiapoptotic = pro-cancer cOncDo2

Normal Cellular Functions for c-Onc-Gene Products (Part 3) (editted from Table 7-3, pp 288-9, Ruddon, 3rd Ed.) Nuclear Transcription Factors myc DNA-binding Protein viral transduction jun DNA-binding Protein viral transduction myb DNA-binding Protein viral transduction cOncDo3

Cell Surface Receptors G-Protein (B) and Enzyme-linked (C) Classes of Cell-Surface Receptors Fig Essential Cell Biology p. 491, Alberts et al. CellReceptors

Figure 5.12a The Biology of Cancer (© Garland Science 2007) p. 131 Mutations or Truncations of Receptor Leading to Misfiring

Figure 5.11 The Biology of Cancer (© Garland Science 2007) p. 130 Truncated Epidermal Growth Receptor in Avian Erythroblastosis

Table 5.2 The Biology of Cancer (© Garland Science 2007) p. 133

Figure 5.12b The Biology of Cancer (© Garland Science 2007) p. 131 Autocrine Stimulation

Figure 5.12c The Biology of Cancer (© Garland Science 2007) p. 131 Stained for Epidermal Growth Factor Receptor (EGF) (Red) Stained for Transforming Growth Factor –alpha (a ligand for EGF receptor) (Green) Yellow shows Red and Green Staining in the Same Cells (Autocrine Stimulation Loop) Autocrine Stimulation in Invasive Breast Carcinoma in Humans

Please send in your name under “Send User Data” Enzyme-linked membrane receptors that normally transfer signals across the cell membrane in response to external signals can go wrong in cancer cells by a variety of ways. Give any one way in which such receptors can be messed up in cancer cells. 0 of

Receptor Tyrosine Kinase Activation (Enzyme-linked Receptor Activation) Figure 15-28, Essential Cell Biology, p. 505, Alberts et. al EnzymeReceptor

Activation of RAS Protein by Activation of Receptor Enzyme Activity; SRC Adapter Protein Functions Figure 15-29, Essential Cell Biology, p. 506, Alberts et al. RASnSRC

Ras Signal Sum

RAS Movie on Weinberg CD

Please send in your name under “Send User Data” Ras-protein as a “molecular switch” that is turned on when it binds a small energy-rich molecule. The bound small molecule that activates Ras-protein is __________________ (give the symbol for the bound molecule). 0 of

G-Protein Activation & Dissociation Fig Essential Cell Biology p. 494 Alberts et. al. GProtAct

Signal Transduction Fig 5-3 GAP = GTPase Activating Protein MAPK = Mitogen-activated Protein Kinase PKA = Protein Kinase A Transduce Signal Transduction: Figure 5-3 McKinnell, p. 141

Nuclear Signaling G-Protein to Nucleus Signal Trnasmission Fig Essential Cell Biology, p. 500 GProt2Nucleus

Normal Cellular Functions for c-Onc-Gene Products (Part 3) (editted from Table 7-3, pp 288-9, Ruddon, 3rd Ed.) Nuclear Transcription Factors myc DNA-binding Protein viral transduction L-myc DNA-bindng Protein? Gene Amplification jun DNA-binding Protein viral transduction fos Transcription Factor with c-jun viral transduction erbA Thyroxine hormone receptor viral transduction ets DNA-binding Protein viral transduction myb DNA-binding Protein viral transduction lyl-1 DNA-binding Protein Chromosome translocation cOncDo3

Prognostic

Normal Cellular Functions for c-Onc-Gene Products (Part 1) (editted from Table 7-3, pp 288-9, Ruddon, 3rd Ed.) Growth Factors sis Platelet-derived GFviral transduction int-2Fibroblast GF-relatedviral insertion int-1Growth factor?viral insertion Growth Factor Receptor, Tyrosine Kinase Activity erbBEpidermal GF receptor (truncated)viral transduction fmsColony-stimulating GF receptor (mutated)viral transduction trkNerve GF receptor? (truncated)DNA transfection neuReceptor-like (unknown ligand)DNA transfaction kitStem-cell GF receptor (truncated)viral transduction Non-receptor, Cytoplasmic Tyrosine-Kinase Activity srcMembrane-associatedviral transduction fps/fesviral transduction yesMembrane-associatedviral transduction abl/bcr-ablviral transduction fgrMembrane-associatedhomology to src cOncDo1

G-Protein Inactivation G-Protein Inactivation Fig Essential Cell Biology, p. 495 Alberts et. al. GProtInactive