oncogenes and tumour suppressors Flashcards
experiment in chickens - cancer viruses
- They took some DNA from chickens and they took some DNA from a virus that is known to cause cancer in the chickens.
they cooked them up together, but heated them up and then they cooled them down - and they said what they were looking for is a duplex.
- So when the chicken DNA comes back together with the viral DNA you can detect it.
○ you can detect if it’s if it’s stuck to it
○ if it’s stuck to it, it means it’s identical or very similar.
This is basically the evidence that There’s a gene in the virus that matches the gene in the chicken.
- So these chickens will develop a sarcoma when they’re infected with this virus.
oncogene
an oncogene is the mutated form of the proto-oncogene.
cause increased cell proliferation
arise by gain of function mutation in a proto oncogene
virus capture of proto oncogenes
viruses go in to the genome and they insert their DNA into the genome
- , and then they come out again and then go in again and come out again as they replicate as they go through their life cycle.
- And sometimes depending on where they go in they can bring bits of DNA back
- if they bring back a piece of DNA that’s got some value like a proto-oncogene, when it infects the next cell it might be able to use that genes to Tell the cell to proliferate faster
- when it proliferates faster. It’s going to make more virus faster.
- So its advantage to the virus
- so you can get this this sort of transduction of the virus
what actually happens when it comes out it invariably gets damaged, So the function changes their or through a number of generations, it’s likely to become mutated.
Bcr-Abl fusion protein
- N - terminal sequences of Abl are missing
- fusion protein is active tyrosine kinase
- activates the RAS signalling pathway
- suppresses apoptosis
- BCR - Abl is an activated form of Abl
types of proteins that are associated with cancer
transcripiton factors
kinases
signalling molecules
cell death regulators
bcr abl fusion protein functions in a cancer cell
Normally the bcr Abl protein at fusion protein functions in a cancer cell to phosphorylate a substrate or Target protein
- and the way it does that is it takes a phosphate group from ATP, which binds to it, and transfers that phosphate group to its Target substrate protein
- the target substrate protein, then changes its shape and goes on to stimulate cell growth of the leukemia cells.
philadelphia chromosome
- This abnormal chromosome Philadelphia chromosome is found in leukemia cells
a particular form of leukemia called CML
gleevac drug
Gleevac drug mimics ATP.
○ It binds to the site within the BCR Abl, ATP normally binds that and it prevents ATP from binding
thereby preventing phosphorylation of the substrate Target protein and and prevents cell growth.
tumour suppressor genes
fusion of normal cells with cancer cells suppresses the cancer
- these genes suppress the formation of tumours
brakes on the cell cycle
negatively regulate the cell cycle
retinoblastoma
- malignant tumour of the developing retina
- null mutation of the RB gene - born with a loss of one of the alleles of this gene
- RB is a tumour supressor
- additional mutation often required
- RB is a transcriptional repressor
- regulates cell cycle - G0-G1
- loss of RB results in proliferation
RB protein
RB protein is bound to the transcription factor
- Stops it from activating the genes
- Then when it is phosphorylated, it lets it go and it can go and switch on genes that drive the cell cycle
- So if you lose RB, then you lose the repression
- So lots of E2F released and it can switch on the genes
So basically the role of RB is to hold back the cell cycle
hereditary form of this disease
- There is a deletion on the other copies
- So loss of one allele
- The other allele can be lost in the retina
- For some reason, for patients that have this mutation it shows up first in the retina
○ This is the first germline mutation - Then there is a second somatic mutation
○ A mutation occurring in one of the cells in your body somewhere else
○ Cant be passed on - not hereditary - doesn’t occur in germ cells
p53
- tumour suppressor
- transciption factor
- suppreses G1 to S phase
- cells arrest in G1 upon DNA damage
- induces P21 - Cell cycle inhibitor
- induces apoptosis
- deletion leads to cell survival and loss of G1 arrest
receptor tyrosine kinases
- extracellular region binds ligand
- transmembrane region
- intracellular tyrosine kinase domain
blocking HER2 activity
pertuzumab
- inhibition through dimerisation inhibition
trastuzumab
- inhibition through direct antibody binding
