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