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Printable Handouts
Navigable Slide Index
- Introduction
- The study of DNA virus transformation revealed how the cell cycle was regulated
- The beginnings: cottontail rabbit papillomavirus (CRPV)
- Polyomaviruses were identified in 1953
- Are the polyomaviruses really cancer viruses?
- The classic DNA tumor viruses: monkey polyomavirus SV40 and mouse polyomavirus
- Key observations from tissue culture infections
- Polyoma & papilloma infections cause rare tumors & transforming events in some cell types
- Viral T antigens and their genes were found in tumors and transformed cells
- When the tumors/ transformed cells were probed for viral DNA, most of the viral DNA was missing!
- More T antigens from two different DNA viruses
- The T antigens: expressed in transformed cells but were found to be viral proteins
- Two key SV40 T antigen observations
- More seemingly unconnected discoveries
- The cell cycle link between T- antigens, Rb, E2F and p53
- A decision to turn on the cell cycle is determined by nutrient concentration and growth factors in media
- If conditions are not right, the cell cycle pauses at the restriction point
- Now comes the time of great insight
- Many DNA viruses need cells in S phase so they can use host enzymes to replicate their own DNA
- The viral T antigens bypass normal cell regulatory control of Rb phosphorylation - how?
- Viral T antigens bypass the cyclins and CDKs to start the cell cycle so the viral genomes can replicate
- The decision to go into S phase is under more control
- P53: the master gate-keeper of the cell cycle
- DNA viruses move the cells into S phase by releasing the repressive complex of Rb and E2F
- Inactivation of p53 by adeno, papilloma and polyoma proteins
- Inactivation of p53 by adeno, papilloma and polyoma proteins
- Links between DNA virus biology and transformation
- The rest of the story...
- Two more mysteries remained
- Transformation is rare and required at least two low probability events
- These events, while exceedingly rare, are dominant
- Transformation is an epiphenomena of the unique life-style for some DNA viruses (1)
- Transformation is an epiphenomena of the unique life-style for some DNA viruses (2)
- Other important DNA viruses associated with tumors (1)
- Other important DNA viruses associated with tumors (2)
- The gamma herpesvirus latent infection
- Gamma herpesvirus and cancer
- Most people in the world are infected with EBV, a gamma herpesvirus
- Cancer is a rare side reaction of the normal process of gamma herpes virus replication
- The big picture of viral transformation and oncogenesis
- Fundamental studies of viruses taught us how cell growth is controlled
Topics Covered
- DNA viruses and transformation
- Viral T antigen and cell cycle control
- The linkage between Cell cycle, T antigens, Rb, E2F and p53
- Transformation as an epiphenomenon of DNA viruses
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Talk Citation
Enquist, L.W. (2020, November 30). Virology and cancer biology: DNA viruses associated with transformation and tumor formation. The discovery of tumor suppressor genes [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 4, 2024, from https://doi.org/10.69645/MHPS3555.Export Citation (RIS)
Publication History
Financial Disclosures
- Lynn Enquist has no commercial/financial relationships to disclose.
Virology and cancer biology: DNA viruses associated with transformation and tumor formation. The discovery of tumor suppressor genes
Published on November 30, 2020
47 min
Other Talks in the Series: The Molecular Basis of Cancer
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, my name is Lynn Enquist,
I'm a professor of molecular biology at Princeton University.
Today, I want to continue my discussion of virology in cancer biology.
In particular, I want to talk to you about
DNA viruses that are associated with transformation in
tumor formation and focus on
the early work that led to the discovery of tumor-suppressor genes.
0:24
If we recall from the previous lecture, on the left side of this slide
I discussed how retroviruses that cause
tumors were discovered, and our basic understanding of how they
cause cells to grow out of control, and how they came together
in the 1960s and '70s to give us this unified theory of cell growth control.
Today, I want to talk about the study of DNA virus transformation.
They didn't reveal much about oncogenes, but rather
they revealed how the cell cycle was regulated.
This started in the 1920s with
the discovery of some viruses that caused tumors in animals, in the 1930s,
discovering warts caused by a papilloma virus in rabbits,
in the late 1950s and early 1960s
how certain DNA viruses transform cells in vitro , and the discovery of polyoma virus.
1:19
The beginnings were the discovery of a virus that was
involved in the formation of papillomas in cottontail rabbits, it's called CRPV.
A papilloma is a benign epithelial tumor that essentially causes warts.
You can see on the head of this cottontail rabbit
these growths, these fibromas that were growing out.
It was benign, the tumors didn't directly kill the animal,
but they interfered with feeding and breathing and everything.
They were very obvious, and in 1933
Richard Shope and Weston Hurst discovered the fact that if they ground up these warts,
made cell-free filtrates and injected the filtered material into rabbits,
they could transmit the capacity to form these fibromas.
Once again, a filterable agent was involved in tumor formation.
At this time, they had a better understanding what a virus was
and so they figured out it must be due to a virus that caused this particular tumor.
Even though they were onto this very early,
it took at least 18 or 20 or so years to characterize what the virus was.
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