TSG as anti-cancer therapies

Question 1

Difference between care takers and gate keepers

Answer 1

Care taker = repair damages, not all mutations are repairable
Gatekeepers = control proliferation and cell

Question 2

What is the role of APC and which cancer is correlated with it

Answer 2

APC is a TSG, a part of Wnt-signaling
When no signal is present APC ubq b-catenin for degradation. When the cell get Wnt signaling APC releases b-catenin which accumulates in the nucleus and transcribe Myc and Cyclin D. In familial polyposis (colorectal cancer) mutated APC cannot block B-catenin which constantly stimulate proliferation. This increase of B-catenin also affect E-cadherin and the cells lose their contact dependence so they can migrate and create polyps

Question 3

How does Hypoxia induce growth factors

Answer 3

When a cell got enough oxygen, an oxygen dependent enzyme propylhydroxylase is active and degrades HIF-1a, without oxygen HIF-1a is accumulates and gets to the nucleus where it transcribe VEGF etc.

Question 4

Common mutations in the cell cycle regulation

Answer 4

• Rb –> blocks E2F
• p53 –> sensescence and DNA repair
• Ras –> driver of the cell cycle (intra cellular cascade kinase)
• CDKs –> bind to cyclins and phosphorylate Rb in different stages so E2F can be free
• Mdm2 –> blocks p53 and degrade it

Question 5

Why is apoptosis important, what is the result of increase vs decrease in apoptosis

Answer 5

importance of apoptosis: tissue homeostasis, removing damaged or infected cells, removal of blood cells and morphogenesis
Too little apoptosis –> disease due to less cells
too much apoptosis –> cancer

Question 6

pro/anti-apoptotic proteins

Answer 6

anti-apoptotic / pro-survival = Bcl, Mcl

pro-apoptotic = Bax family - Bax, Bak, Bok. BH-only family - Bid, Bad, Puma

Question 7

Explain the intrinsic apoptotic pathway

Answer 7

Induced by intracellular stress, damage, infection etc.

Pores in the mitochondria causes a release of Cytochrome C which binds to Apaf-1 and creates the Apoptosome (wheel of death). Pro-caspase 9 cleaves itself by binding to the apoptosome and thereby a lot of caspases gets activated. Every step can be inhibited by Smac/DIABLO also released by the mitochondria

Question 8

Explain the extrinsic apoptotic pathway

Answer 8

Induced by intracellular stress or damage recognized by other immune cell, inducing death by contact

FasL is expressed on immune cell when signaling a cell to enter apoptosis. by binding its FasL on the always expressed Fas on the cell. Causing an intracellular cascade where procaspase 8 and 10 is cleaved and further activates other caspases