ENVB 437 Lecture Notes - Lecture 12: Dihydrofolic Acid, Wild Type, Mitosis
4 Jun 2018
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Eukaryotic cells and viruses – lecture 12 (February 14th, 2018)
DNA TUMOR VIRUSES
Slide 2 – in general
- RNA tumour viruses generally exert their effects through growth signalling pathways, turning them on in the
absence of stimuli.
o “add gasoline to the system”
- DNA tumour viruses generally act by sequestering proteins that control cell proliferation (Rb, p53), to shift the
cells into S phase
o “release the brakes”
Slide 3 – DNA tumour viruses
- Diverse group of viruses with different structures, genome organization, and strategies of replication
- Some induce tumours in natural host
o Papilloma
o EBV, KSHV
o Hepatitis B
- Others induce tumours in experimental systems:
o Adenovirus
o Polyomaviruses, SV40* (controversial)
- some of them are associated with tumours, but they have been engineered to have minimal effects on the cell
itself
Slide 4 – DNA tumour viruses
Oncogenic potential linked to virus replication strategy
- Oncogenes are essential viral genes without cellular homologues (for small DNA tumor viruses)
- Transformation occurs ONLY in “aborted” viral life cycle (early genes expressed but replication, which
is cytocidal, does not occur)
o Some of the genes are being expressed from these viruses but not all, because when the virus
replicates, it becomes cytocidal it kills itself tjos strategy
o Adenovirus, SV40, and polyomavirus frequency of transformation is less than 1 in 10 5 infected cells.
o For small DNA tumor viruses, integration of viral genome may enable abortive viral lifecycle.
▪ Normally they do not become a provirus, but incases where they do cause distruption of the
cell cycle; thus this causes the cell to over express certain proteins
find more resources at oneclass.com
find more resources at oneclass.com
Slide 5 – DNA tumour viruses target tumour suppressors
Virus
Gene product
Cellular target
Adenovirus
E1A
E1B
Rb
P53
SV40
Large T antigen
Rb, p53
Polyomavirus
Large T antigen (early)
Middle T antigen
Rb
Src, PI3K
Papillomavirus
E7
E6
E5
Rb
p53
- These DNA viruses are labelled in terms of their functions in terms of what it expresses early (E) in the
infections
- When it replicates it also expresses late genes, responsible for making the viral particles and all that stuff
Slide 6 – Tumour suppressor genes
- They supress the transcription of the gene resulting in an inactive
growth complex
- However, you can displace this receptor with something like a
binding protein
o The binding protein binds to the repressor unit,
displacing it, and allows the growth promoter to be
active
- Or we can phosphorylate the repressor; that’s going to disturb
the association between the two units
- Or a mutation could occur that would change the repressor
protein in such a way that is no longer has a recognition
sequence for the promoter
Slide 7 – Tumour suppressor genes
- Fusion of normal cells with tumour cells suppression of
neoplastic properties “tumour suppressor genes”
- Since healthy cells are dominant over tumour cells when it
comes to growth-properties tumour cells have lost
functions associated with tumour suppressors
find more resources at oneclass.com
find more resources at oneclass.com
Slide 8 – tumour suppressor genes acting as cell cycle checkpoints
- Acting as cell cycle checkpoints
- If we have any DNA damage or other stressor:
o P53 is activated
o P53 It is part of a complex which acts as a transcription
factor
o If p53 is activated, you get increased levels of p21
▪ This binds to CDK which are required in the
cell cycle
▪ When CDK2 complex
▪ That will phosphorylate Rb which is bound to
E2F
• It is now free as an active transcription
factor which is active in DNA
synthesis and allows the cell to go
from G1 to S phase
Slide 9
- Retinoblastoma
Slide 10
2 types:
- 40% genetic – 1 parent carrier
o 50% risk
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Eukaryotic cells and viruses lecture 12 (february 14th, 2018) Rna tumour viruses generally exert their effects through growth signalling pathways, turning them on in the absence of stimuli: add gasoline to the system . Dna tumour viruses generally act by sequestering proteins that control cell proliferation (rb, p53), to shift the cells into s phase: release the brakes . Diverse group of viruses with different structures, genome organization, and strategies of replication. Some induce tumours in natural host: papilloma, ebv, kshv, hepatitis b. Others induce tumours in experimental systems: adenovirus, polyomaviruses, sv40* (controversial) some of them are associated with tumours, but they have been engineered to have minimal effects on the cell itself. Oncogenes are essential viral genes without cellular homologues (for small dna tumor viruses) Slide 5 dna tumour viruses target tumour suppressors. These dna viruses are labelled in terms of their functions in terms of what it expresses early (e) in the infections.
