Oncogenes and TSG Flashcards
How can viruses cause cancer
- Virus can transmit oncogenes between cells when incorporating these into the new host
- Virus can integrate viral promoters near oncogenes, making them over express
RAS mutation in cancer
Gly–>Val in GTP binding pocket, keeping the enzyme in an active state where it has bound GTP
Myc mutation in cancer
Burkitt’s lymphoma; Myc is placed under the control of the IgH promoter, that is highly expressed in Africa
Oncogene mutations
- Point mutations; making them more active
- Gene amplification, but the protein is normal
- Chromosomal rearrangement; something placed infront of the gene or fusion protein produced
What is Rb
Gate keeper gene (TSG), inhibit entry into S-phase from G1 phase. cyclins have to phosphorylate Rb in two steps so it can release E2F transcription factor. In tumors Rb is often dysfunctional so E2F is always active and S-phase is induced.
what is the role of p53
Guardian of the genome, TSG. Gets activated upon stress, DNA damage (ATM activation phos. p53) etc.
- Stops cell cycle by producing p21 that inhibit CDKs and keep Rb active
- DNA repair,
- Blocks angiogenesis
- Induces apoptosis by producing Bax, Fas, Puma
- Transcription factor
What is the role of Myc
- Oncogene
- Transcription factor; If bound to Max it bind to DNA and activate a lot of genes for cell cycle, metabolism, protein biosynthesis –> everything needed for cell growth and cancer development
- Myc can also cause apoptosis, oncogene-induced senescence and DNA damage response
How is Senescence caused
- Telomere dysfunction
- Oncogene activation (ras)
- Cell culture, cell-cell contact inhibition
- Oxidative stress
- cytotoxic drugs