Practice Questions Flashcards
Why is Cancer so difficult to treat? (10)
- Self (hard to target, hidden from immune)
- Therapies require active apoptotic pathways
- Core is hypoxic (hard to get drugs in/radio needs O2)
- Hetrogenous nature (no clear boundaries/therapy doesn’t work for every cell)
- Detected late, metastases likely
- Invasive and spreads easily (grow back from one cell)
- Caused by many different things
- Polygenic so need to target many proteins
- If therapy is not 100% effective it can reseed
- Resistance through binding/efflux pump expression
How can a mutation in Src make in constitutively active?
What is the role of viruses in this discovery?
Wild type Src: when C terminal Y is phosphorylated the molecule folds up and is inactive (catalytic domain is no accessible). When dephosphorylated the protein unfolds and becomes active.
In mutated Src the terminal Y may be missing so the molecule cannot be phosphorylated and is therefore constitutively open and active.
First identified in chickens, when the virus replicates it excises Src minus the Y. Also on reinfect in the gene for constituatively active Src is induced.
Bcl2
bcl-2 – anti apoptotic, proto- oncogene. Inhibits Bax to prevent membrane pores. In cancer often translocated to region of high expression (eg in B cell lymphoma next to Ig enhancer). Tilts cell balance in favour of survival.
pRb
pRb – tumour suppressor involved in regulating cell cycle. G1 checkpoint. In resting cells binds E2F to prevent transcription. Following GF stimulation Pn of pRb by CDK4/6 causes release of E2F and cell cycle progression. In cancer LoF of pRb decreased protein expression and increased levels of free E2F.
Ras
Ras – proto-oncogene involved in cell proliferation Ras-MAPK . Normally hydrolyses GTP to GDP and during process activates Raf. Point mutation in Ras makes it constitutively active by destroying hydrolysing activity. Const. bound to GTP and active.
