Midterm 2 - Notes 4 (Part 2) Flashcards
What are 4 possible mechanisms that can over-activated a gene?
- Mutation in coding region
- Mutation in promoter/enhancer
- Gene amplification
- Chromosomal rearrangements
Mutation in coding region
Deletion or point mutation
- has potential to change the protein
Mutation in promoter/enhancer
Regulatory mutation
- do not effect the protein activity itself, but changes that expression level
- greatly overproduced
Gene amplification
Having multiple copies of the same gene
- all normal sized, just over expressed
Chromosome rearrangment
Can cause over production
- may lead to fusion gene
What are the 6 steps in metastasis?
- Normal epithelium
- Cells grow as benign tumour in epithelium
- Cells become invasive and enter capillaries
- Adhere to blood vessel wall in liver
- Escape from blood vessel to form micro-metastasis
- Colonize liver, forming full blown metastasis
Fusion gene
Is a hybrid gene formed from 2 previously separated genes
What do proto oncogene to oncogenes mutations derive from? (2)
- Loss of regulation on protein level
- post translational modification - Miss regulated expression
- over expression
What are 4 possible mutations that lead to LOF of a gene in the first allele and 6 in the second allele? (10 in total)
First allele
1. Mutation in coding region protein non-functional
2. Deletion
3. Mutation in promoter/enhancer
4. Epigenetic silencing
Second allele
5. Non disjunction causes chromosome loss
6. Chromosome loss, then chromosome duplication
7. Mitotic recombination event
8. Gene conversion during mitotic recombination
- repair mechanism
9. Deletion
10. Point mutation
What is the most common mechanism for LOF of a gene?
Epigenetic silencing
- no longer able to transcribe and this gets inherited from cell to cell
Mitotic recombination
Parts of one chromosome being replaced by the other chromosome
What can point mutation cause?
Frame shift mutation
- insertion/deletion
Whats an example of a rare hereditary form of cancer used to identify tumour?
Retino blastoma (RB)
Herediltary
Past on from generation through germ line and able to trace mutation through those generations and is common to develop a tumour
Non-hereditary
Random mutation typically from the environment and is not typically passed on and doesnt always form a tumour
What does Rb encode for?
Protein protein interaction
What does Rb do when it interacts with E2F?
E2F gets inactivated when bound to Rb
What does Rb/E2F inhibit?
S-phase gene expression
- is a block that prevents cells from entering into the S-phase
What is Rb?
A suppressor of E2F
What family does E2F belong to?
TF
What does E2F do?
It activates transcription of many S-phase related genes
What is E2F?
Is a major switch activation S-phase
What phosphorylates Rb? (2)
- Cyclin D-CDK4
- this activates E2F - S-CDK
What inhibits cyclin D-CDK4 activity?
P16
What activates a signalling cascade?
Mitogen binding activity
What does mitogen binding activity lead to?
The activation of S-CDK
- which is a specific protein kinase
S-CDK
S-Phase cyclin dependent kinase
What does E2F activate?
Transcription of S-phase specific genes
- cell enters S-phase
What happens if you lose the function of Rb?
The E2F gets activated and you lose to G1-S checkpoint
- uncontrolled activation
When does Rb get inactivated?
When it gets phosphorylated
