The Discovery And Function Of Oncognes And Tumor Suppressor Flashcards Preview

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Flashcards in The Discovery And Function Of Oncognes And Tumor Suppressor Deck (11)
0

RNA virus morphology

Types A-D
Differences are minor and do not effect the life cycle
Differences are based on the appearance of the electron dense core
A-> intracellular, no know role
B,C,D->virus particles
B-> eccentric cores
C-> centric cores 90%
D-> bullet shaped cores
Overall composition:
60-70% protein
20-30% lipid
2% carbs
1% RNA

1

Formation of RNA tumour virus proviral DNA

RNA genome-> single stranded
-> copied using reverse transcriptase with the host tRNA as a primer
-> RNA DNA hybrid produces and cut to correct size
->Host RNase cuts up the RNA to produce short primers for DNA synthesis
-> DNA polymerase produces a double stranded copy
-> double stranded proviral DNA copy enters the nucleus and integrated into the host chromosome
-> only a small sequence so can be inserted in many areas
-> transcribed with host genes
Acts as a template for new viral mRNA

2

New viral mRNA

Is produced from ds provial DNA template
-> act as mRNA to allow viral protien synthesis
-> act as new RNA genome in new particles-> formed when the viral proteins and mRNA collect at the cell membrane and bud
Can infect and pick up oncogenes from us

3

How do viruses initiate cancer?

Slow transforming viruses-> insert viral-derived DNA randomly in to the genome-> by chance next to a proto oncogene-> viral DNA causes abnormal promotion of proto oncogene
Acute transforming viruses-> contain a viral oncogene-> when inserted in to host genome is expressed leading to neoplasia
Sarcoma:
May carry an oncogene which is then turned on when inserted near an LTR (promoters)
LTR is a strong promotor of sarcoma (src) which is brought in NPY the virus
Leukaemia:
LTR turns on an oncogene that should be switched off
A silent human oncogenes is collected by virus and inserted near and LTR

4

LTR

Long tandem repeats
Contain elements necessary for transcription
-> promotors, enhancers, stop and start signals

5

Function of oncogene products

Oncogenes tend to effect the growth cycle either by causing inappropriate cell division or preventing apoptosis
-hormone like-> v.sis-> produces a hormone almost identical to PDGF-> alters ligand at receptor so always active
-receptor like-> v erb -> produces an identical receptor to EGFR-> always active
-G-protien like-> Ras-> mimics G protein-> no hydrolysis of GTP to turn off growth
-transcription factors> myc-> essentially identical to transcription factors

6

Oncogenic DNA viruses

Papilloma viruses-> many subgroups-> common warts of SV 40 polyoma-> produce proteins that inactivate certain products of tumour suppressor cells
Adenovirus-> possibly 15 human oncogenic types
Herpesvirus-> Epstein Barr in humans types 1 and 2

7

DNA virus life cycles

Two life cycles
Lytic-> normal
permissive cells
early and late phases (early and late phase genes)
new viruses produced
host cell lysis
Transforming-> bad
Non permissive cells-> don't let virus grow
Only early phase reactions
No new virus released
Host cell continues to divide

8

DNA virus life cycle stages

Early gene expression in SV 40->
Half the viral genome is transcribed into a single mRNA-> 19s RNA produced-> codes for T antigen-> switches on he late genes
Early gene expression continues-> late genes are transcribed-> late gene RNA codes for VPI 1,2,3

9

Knudsons hypothesis

Studies on families with retinoblastoma
Sporadic pattern-> two genes needed to be switched off
Loss of function at Rb
-> born with only one active gene so only waiting for one to get switched off-> higher chance
-> loose normal chromosomes in cell replication
-> loss/replication of abnormal gene
-> mitotic crossing over
-> mutation
Family dominantly inherited pattern-> p53 is inactive

10

Normal cell behaviour can be effected by:

1) loss of function of both antioncogenes
2) loss of function of antioncogene protien products-> DNA viral proteins interact with (T antigen) or actually degrade (e6 from papilloma virus) the protein products
3) activation of over expression of a previously silent oncogene

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