Oncogenes and tumour suppressor genes Flashcards
What is a oncogene in terms of function?
= gain of function
- An altered gene whose product can act in a dominant fashion to help make a cell cancerous
- Oncogene = mutant form of normal gene (proto-oncogene)
What is a tumour supressor in terms of function?
= loss of function
A gene whose normal activity prevents formation of a cancer
How can a proto-oncogene be transferred into a normal growth-stimulating protein or resistant protein?
How can a proto-oncogene become a bad protein?
via activation
What is the RAS oncogene family?
RAS proteins are normally bound to GDP in a neutral state
Oncogenic activation of RAS is seen in about 30% of human cancer
How does the normal RAS pathway differ from the RAS oncogene pathway?
What is the MYC oncogene family?
Belong to family of transcription factors have effects of protein translation, cell-cycle progression and metabolism and cell proliferation, differentiation and survival
MYC oncogene encodes a helix-loop-helix zipper transcription factor that with protein Max, transactivates gene expression –> proliferation
- Activated as a result of chromosomal translocation
How can you get the balance between Growth-promoting pathways and intrinsic tumour suppressor pathways?
Loss of tumour suppressor gene function requires inactivation of both alleles of the gene
What is the study of Knudson of the retinoblastoma gene?
- rare childhood cancer
- 2 forms: sporadic and familial
Study led to ‘two-hit’ hypothesis:
- development of retionblastoma requires 2 mutations
What happens to the retinoblastoma leading to cancer?
Retinoblastoma’s main binding partner is the E2F transcription factor
The G1 checkpoint in the cell cycle leads to the arrest of the cell cycle in response to DNA damage
- A key substrate for cyclin D is RB protein
When the Rb tumour suppressor is active it can inhibit cell proliferation
When Rb is dephosphorylated/hypo phosphorylation it is active and remains bound to E2F and blocks progression to the S phase
When Rb is hyperphosphorylated, it is inactive
- Leads to no cell cycle arrest and cell cycle progression
How can Rb be inactivated?
What is the P53 tumour supressor?
- ‘guardian of the genome’
- It is involved in sensing DNA damage and regulating cell death/apoptosis
- But it is mutated in 30-50% occurring human cancers
- Can bind to around 300 different gene promotor regions
- Levels of p53 are kept low by MDM2 protein
Therapeutic strategies:
Retro-virus mediated gene transfer of the wild-type TP53 gene into human could lead to the inhibition of tumour cell growth
