Tumor Suppressors

Question 1

Double Strand Break (DSB) Repair

Answer 1

Activates ATM/R (can act at multiple points) which stabilizes/activates p53. p53 activates p21 which inhibits CDK2, blocks Rb phosphorylation, and stops cell cycle progression
ATM also activates Chk1/2 and BRCA1/2 to initiate repair

Question 2

2 Different General Mechs to Stop Further Replication

Answer 2

Apoptosis by p53 if DSBs/other damage can’t be repaired

Senescence pathway via p16(INK4)/p14(ARF) produced by unusual alternative reading frames

Question 3

Cyclin/CDK Cascade to Initiate DNA Synth/Replication

Answer 3

Mitotic/enviro signals elevate cyclin D production, which activates CDK4/6 -> partially phospho Rb -> E2F TF which starts production of cyclin E -> pairs w/ CDK2 -> completes (+) feedback loop to fully phospho Rb (can pass R) -> rest of E2F, which produces cyclin A. A pairs with CDK2 to ensure complete DNA synth

Question 4

p27

Answer 4

Elevated by cell-cell junctions & inhibits CDK2 to block cells from overexpanding. Commonly lost in breast cancer

Question 5

TGF Beta R

Answer 5

Activates Smad dimers which can elevate p27 and upregulate p16(INK4)

Question 6

PKB/AKT 2 Cell Cycle Progressive Effects

Answer 6

Blocks apoptosis via Bcl2 activation

Promotes cell cycle progression by inhibiting p21 and p27

Question 7

2 Things that Elevate p16/14

Answer 7

TGF Beta and c-myc

Question 8

MDM2

Answer 8

Destroys p53 until p53 phospho’d by ATM

Question 9

p53 Initiation of Apoptosis

Answer 9

Elevates Bax which opens mt channels, allowing cyt-C release and caspase cascade induction. Bcl-2 blocks Bax

Question 10

3 Effects of myc gene Activation

Answer 10

Activated by MAPK cascade, can:
Increase cyclin D production/activation of CDK4/6
Degradation of p27, enhancing CDK2 activity
Increase E2F production

Question 11

Cell Mech to Guard Against myc Overexpression

Answer 11

Excessive myc also increases p14ARF, stabilizing p53 and inducing apoptosis or cell cycle arrest

Question 12

PKB/AKT

Answer 12

Upregulates Bcl2 blocking apop, but can also block p21 and p27, inhibiting p53 effects and cell-cell junction tumor suppressive effects

Question 13

PTEN

Answer 13

Blocks PI3K to prevent activated PKB/AKT. So a lot of tumors involve a mut of this

Question 14

Telomerase

Answer 14

Maintains telomeres in most embryonic cells (reverse transcriptase with RNA template), but then is turned off in differentiated cells

Question 15

Breakage-Fusion-Bridge Cycle

Answer 15

Chromosomes without telomeres can form “sticky ends” and attach to others -> aneuploidy, but these are broken with massive changes. Most die, but if they lose p16/p53 checkpoint functions and regain telomerase function, these new chromsomes can become stabilized with massive mutations

Question 16

APC/C

Answer 16

Only allows cells to pass from metaphase-anaphase when properly lined up. If mut, can get aneuploidy. Messed up in some colon cancers