elo173 slide viral oncogene
Genome of Hepatitis B Virus
VIRAL ONCOGENE
Dr. Yahwardiah Siregar, PhD
Dr. Sry Suryani Widjaja, Mkes
Biochemistry Department
Proto Oncogen and Oncogen
• Oncogen
– Proteins that possess the ability to cause cellular
transformation.
– Act in a dominant fashion, either overexpression
or activating mutations.
Cellular transformation.
morphologic changes, loss of contact inhibition,
anchorage independent growth, ability to form
tumors when transplanted into nude mice.
• Proto-oncogene.
– Potential to become activated into a cancer
causing oncogene.
– Have been found in all multicellular organisms.
– Would be involved : basic essential functions of
the cell related to control of cell proliferation and
differentiation.
– In normal cell : expression is tightly controlled.
Cell Cycle
• Cell-cycle control system is based on cyclically
activated protein kinases :
• -Cdks ( cyclin dependent kinases )
• -Cyclins ( cdk regulator protein ),without
cyclins cdk is inactive.
Proto-oncogenes
• 1.Growth Factors
– Stimulate cells in stationary stage to enter the cell
cycle.
– Occurs in a two stage process :
• Stimulation to proceed into G1 provided by
PDGF,EGF,followed by progression factors :IGF to
progress through the cell cycle.
– Action via autocrine and paracrine model.
• 2.Growth factor receptors
– Link the information from extracellular
environment (GF) to a number of different
intracellular signaling pathways.
– The most important : transmembrane receptor
tyrosine kinases.
• 3. Signal transducers.
– Cytoplasmic nonreceptor tyrosine kinases.
– Proteins with enzyme activity such as
phospholipase C , PI3-K
– Adaptor proteins : Grb2
– SH2 and SH3 domain.
– Three major pathways : PI3-kinase (PI3-K/AKT
pathway,RAS/mitogen-activated protein kinase
(MAPK) pathway,JAK/STAT pathway.
• 4. Nuclear proto-oncogne and transcription
factors.
– Involved in the control of gene expression by their
action on DNA itself
– Final site of action for messages sent from GF.
– Level at which control of growth and proliferation.
• animasi
Apoptosis
• Programmed cell death
• Intracellular machinery responsible for
apoptosis is called caspases.
• Caspases
• Synthesized in the cell as inactive precursor called
procaspases
• Usually activated by cleavage at aspartic acids by other
caspases.
Mechanisms of oncogene activation
• 1. Structural alteration.
– Point mutations
– Chromosomal translocation
– Truncated form of protein (transition mutation)
• 2. Amplification
• 3. Deregulated expression
– Insertional mutagenesis
– Translocation.
Tumor suppressor genes
• Play an important role in tumorigenesis.
• Involved in the control of abnormal cell
proliferation.
• Loss or inactivation : association with the
development of malignancy.
Viral Oncogene
• Three major mechanisms by which an
infectious agent can cause cancer :
• 1. Persistent infection
chronic
inflammation repeated cycles of cell
damage and cellular proliferation
accumulate genetic mutations
initiation
and promotion of cancer .
• 2.Direct participation of infectious agents in
the transformation of the cell through
activation of cellular oncogene pathway.
• 3. Relevant to HIV : infection may result in
immunosuppression and decreased
recognition of infected or transformed cell by
host immune system.
Retroviruses
Gene
TRANSCRIPTION
Primary
transcript
NUCLEUS
Degradation
MODIFICATION / PROCESSING
mRNA
Degradation
Transport
mRNA
CYTOPLASM
Active
degradation
TRANSLATION
Protein
Degradation
inactive
Mechanisms of retroviral
oncogenesis.
• 1. Slowly transforming viruses.
– Insertional mutagenesis
• 2. Acutely transforming viruses.
– Oncogene transduction
• 3. Trans-acting retroviruses.
– Affect expression or function of cellular growth
and differentiation genes.
• HTLV1 ( the only human retrovirus known to directly
cause cancer).
VIRAL ONCOGENE
Dr. Yahwardiah Siregar, PhD
Dr. Sry Suryani Widjaja, Mkes
Biochemistry Department
Proto Oncogen and Oncogen
• Oncogen
– Proteins that possess the ability to cause cellular
transformation.
– Act in a dominant fashion, either overexpression
or activating mutations.
Cellular transformation.
morphologic changes, loss of contact inhibition,
anchorage independent growth, ability to form
tumors when transplanted into nude mice.
• Proto-oncogene.
– Potential to become activated into a cancer
causing oncogene.
– Have been found in all multicellular organisms.
– Would be involved : basic essential functions of
the cell related to control of cell proliferation and
differentiation.
– In normal cell : expression is tightly controlled.
Cell Cycle
• Cell-cycle control system is based on cyclically
activated protein kinases :
• -Cdks ( cyclin dependent kinases )
• -Cyclins ( cdk regulator protein ),without
cyclins cdk is inactive.
Proto-oncogenes
• 1.Growth Factors
– Stimulate cells in stationary stage to enter the cell
cycle.
– Occurs in a two stage process :
• Stimulation to proceed into G1 provided by
PDGF,EGF,followed by progression factors :IGF to
progress through the cell cycle.
– Action via autocrine and paracrine model.
• 2.Growth factor receptors
– Link the information from extracellular
environment (GF) to a number of different
intracellular signaling pathways.
– The most important : transmembrane receptor
tyrosine kinases.
• 3. Signal transducers.
– Cytoplasmic nonreceptor tyrosine kinases.
– Proteins with enzyme activity such as
phospholipase C , PI3-K
– Adaptor proteins : Grb2
– SH2 and SH3 domain.
– Three major pathways : PI3-kinase (PI3-K/AKT
pathway,RAS/mitogen-activated protein kinase
(MAPK) pathway,JAK/STAT pathway.
• 4. Nuclear proto-oncogne and transcription
factors.
– Involved in the control of gene expression by their
action on DNA itself
– Final site of action for messages sent from GF.
– Level at which control of growth and proliferation.
• animasi
Apoptosis
• Programmed cell death
• Intracellular machinery responsible for
apoptosis is called caspases.
• Caspases
• Synthesized in the cell as inactive precursor called
procaspases
• Usually activated by cleavage at aspartic acids by other
caspases.
Mechanisms of oncogene activation
• 1. Structural alteration.
– Point mutations
– Chromosomal translocation
– Truncated form of protein (transition mutation)
• 2. Amplification
• 3. Deregulated expression
– Insertional mutagenesis
– Translocation.
Tumor suppressor genes
• Play an important role in tumorigenesis.
• Involved in the control of abnormal cell
proliferation.
• Loss or inactivation : association with the
development of malignancy.
Viral Oncogene
• Three major mechanisms by which an
infectious agent can cause cancer :
• 1. Persistent infection
chronic
inflammation repeated cycles of cell
damage and cellular proliferation
accumulate genetic mutations
initiation
and promotion of cancer .
• 2.Direct participation of infectious agents in
the transformation of the cell through
activation of cellular oncogene pathway.
• 3. Relevant to HIV : infection may result in
immunosuppression and decreased
recognition of infected or transformed cell by
host immune system.
Retroviruses
Gene
TRANSCRIPTION
Primary
transcript
NUCLEUS
Degradation
MODIFICATION / PROCESSING
mRNA
Degradation
Transport
mRNA
CYTOPLASM
Active
degradation
TRANSLATION
Protein
Degradation
inactive
Mechanisms of retroviral
oncogenesis.
• 1. Slowly transforming viruses.
– Insertional mutagenesis
• 2. Acutely transforming viruses.
– Oncogene transduction
• 3. Trans-acting retroviruses.
– Affect expression or function of cellular growth
and differentiation genes.
• HTLV1 ( the only human retrovirus known to directly
cause cancer).