Transcript Functions of Onc-Gene Products: Signal Transduction, Cell

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 GF
• int-2 Fibroblast GF-related
viral transduction
viral insertion
Growth Factor Receptor, Tyrosine Kinase Activity
• erbB Epidermal GF receptor (truncated)
• fms Colony-stimulating GF receptor (mutated)
• neu Receptor-like (unknown ligand)
• kit Stem-cell GF receptor (truncated)
viral transduction
viral transduction
DNA transfaction
viral transduction
Non-receptor, Cytoplasmic Tyrosine-Kinase Activity
• src Membrane-associated
• abl/bcr-abl
viral transduction
viral 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/mil
viral transduction
• mos
viral transduction
Membrane Associated G Proteins
• H-ras & GTP-binding GTPases
K-ras
• N-ras
GTP-binding GTPase
viral transduction & DNA
transfection
DNA 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
• jun
DNA-binding Protein
• myb
DNA-binding Protein
viral transduction
viral transduction
viral transduction
cOncDo3
Cell Surface Receptors
G-Protein (B)
and Enzyme-linked (C)
Classes of Cell-Surface
Receptors
Fig. 15-12
Essential Cell Biology
p. 491, Alberts et al.
CellReceptors
Mutations or Truncations of Receptor Leading to Misfiring
Figure 5.12a The Biology of Cancer (© Garland Science 2007)
p. 131
Truncated Epidermal Growth Receptor in Avian Erythroblastosis
Figure 5.11 The Biology of Cancer (© Garland Science 2007) p. 130
Table 5.2 The Biology of Cancer (© Garland Science 2007) p. 133
Autocrine Stimulation
Figure 5.12b The Biology of Cancer (© Garland Science 2007)
p. 131
Autocrine
Stimulation in
Invasive Breast
Carcinoma in
Humans
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)
Figure 5.12c The Biology of Cancer (© Garland Science 2007)
p. 131
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.
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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).
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G-Protein Activation
G-Protein Activation
& Dissociation
Fig 15-15
Essential Cell Biology
p. 494
Alberts et. al.
GProtAct
Signal Transduction: Figure 5-3
McKinnell, p. 141
Signal Transduction Fig 5-3
GAP = GTPase Activating Protein
MAPK = Mitogen-activated
Protein Kinase
PKA = Protein Kinase A
Transduce
Nuclear Signaling
G-Protein to Nucleus
Signal Trnasmission
Fig. 15-22 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
• L-myc DNA-bindng Protein?
• jun
DNA-binding Protein
• fos
Transcription Factor with c-jun
• erbA
Thyroxine hormone receptor
• ets
DNA-binding Protein
• myb
DNA-binding Protein
• lyl-1
DNA-binding Protein
viral transduction
Gene Amplification
viral transduction
viral transduction
viral transduction
viral transduction
viral transduction
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 GF
• int-2 Fibroblast GF-related
• int-1 Growth factor?
viral transduction
viral insertion
viral insertion
Growth Factor Receptor, Tyrosine Kinase Activity
• erbB Epidermal GF receptor (truncated)
• fms Colony-stimulating GF receptor (mutated)
• trk Nerve GF receptor? (truncated)
• neu Receptor-like (unknown ligand)
• kit Stem-cell GF receptor (truncated)
viral transduction
viral transduction
DNA transfection
DNA transfaction
viral transduction
Non-receptor, Cytoplasmic Tyrosine-Kinase Activity
• src Membrane-associated
• fps/fes
• yes Membrane-associated
• abl/bcr-abl
• fgr Membrane-associated
viral transduction
viral transduction
viral transduction
viral transduction
homology to src
cOncDo1
G-Protein Inactivation
G-Protein
Inactivation
Fig. 15-16
Essential Cell
Biology,
p. 495
Alberts et. al.
GProtInactive