Cell Cycle, Apoptosis, and Cancer

Question 1

Myc/Retinoblastoma Pathway

Answer 1

Myc upregulates G1-CDK; CDK phosphorylates Rb; Rb-P releases E2F; E2F (TF) drives cell from G1 to S

Question 2

What cyclins and kinases are needed for Rb pathway?

Answer 2

CDK-4 and CDK-6 with Cyclin D

Question 3

What genes do E2F promote transcription of?

Answer 3

Cyclin E for transition to S and Cyclin A for Synthesis stage; also upregulates CDK-2 which hyperphosphorylates Rb more

Question 4

Phosphorylates T loop, bringing the cyclin-CDK complex to full activity

Answer 4

CDK-activating Kinase (CAK)

Question 5

Cyclins and CDKs during each part of interphase

Answer 5

G1 - Cyclin D; CDK-4 and CDK-6
G1/S - Cyclin E; CDK-2
S - Cyclin A; CDK-2
G2 - Cyclin A and Cyclin B; CDK-1

Question 6

Inhibits CDK via phosphorylation of roof site

Answer 6

WEE1

Question 7

Reactivates CDK via dephosphorylation of roof site

Answer 7

Cdc25

Question 8

Binds both CDK and cyclin to lower activity

Answer 8

P27(kip1); early cell cycle events

Question 9

APC pathway

Answer 9

activated by binding of CDC20; APC poly-ubiquinates cyclins S and M; cyclins targeted for destruction in proteasome; less cyclins downregulates CDKs

Question 10

E3 ubiquitin ligase that regulates p53

Answer 10

MDM2

Question 11

p53 pathway

Answer 11

if DNA damage p53 is phosphorylated; no longer degraded and can upregulate CKI p21; leads to cell cycle arrest

Question 12

binds and inactive cyclin-CDK complexes keeping Rb hypophosphorylated (inactive); transcription influenced by p53; mainly CDK-2!

Answer 12

p21

Question 13

Forms a pore in the mitochondrial membrane in response to a pro-apoptotic stimulus

Answer 13

BAX

Question 14

Intrinsic Pathway

Answer 14

BAX forms hole in mitochondria; cytochrome C leaves and binds with Apaf1 forming apoptosome; apoptosome activates caspase 9 which activates caspase 3,6, and 7

Question 15

Extrinsic Pathway

Answer 15

TNF-alpha or Fas receptors activated; procaspase 8 cleaved; caspase 8 activates 3, 6, and 7

Question 16

HER2 receptor as oncogene

Answer 16

Valine to Glutamine in RTK domain causes dimerization without a ligand (NEU); leads to breast cancer

Question 17

EGF receptor as oncogene

Answer 17

deletion in RTK domain causes constitutionally active receptor (EGFRVIII); leads to glioblastoma

Question 18

BCR-ABL translocation

Answer 18

translocation of ABL on 9 and BCR on 22 (Philadelphia chromosome); leads to BCR-ABL fusion protein; causes chronic myelogenous leukemia (CML)

Question 19

Tumor Suppressor Functions

Answer 19

Repress cell cycle progression
Promote apoptosis
Couple DNA damage to the cell cycle
DNA repair proteins

Question 20

Common tumor suppressors

Answer 20

RB1 encodes RB
TP53 encodes p53
PTEN - phosphate and tensin homolog
APC - adenomatous polypsis coli

Question 21

Cell adhesion proteins that prevent tumor cells from dispersing, block loss of contact inhibition, and inhibit tumor metastasis

Answer 21

Metastasis Suppressors

Question 22

Antibody therapy directed towards HER2; blocks cleavage, dimerization, activates Ab mediated cytotoxicity, or internalizes HER2 for degradation

Answer 22

Trastuzumab (Herceptin)

Question 23

Binds where ATP normally would on BCR-ABL enzyme, preventing CML

Answer 23

Mesylate (Gleevac)

Question 24

Interphase steps

Answer 24

G1: RNA and protein synthesis for DNA replication
S: DNA synthesis
G2: DNA stability is ensured for mitosis