Lec 6 cell cycle, apop, cancer

Question 1

Cell cycle and its checkpoints

Answer 1

Question 2

What happens at the restriction point (R)

Answer 2

if growth factors are limiting restriction occurs

2hours before

many diff growth factors

Question 3

what happens at the G1 checkpoint?

Answer 3

timing sim to restrcition point (2 hr)

occurs in response to DNA damage

Question 4

what is checked at the G2 checkpoint?

Answer 4

verify complete genomic duplication

Question 5

what happens at the metaphase checkpoint

Answer 5

ensures chromosomes attached to mitotic spindle

Question 6

explain the steps that drive cell proliferation

Answer 6

• Myc-Transcription factor that drives cell prolif
• Myc increases G1-cyclin-dependent kinases (CDK)
• CDK phosphorylates retinoblastoma (Rb)
• Phospho-Rb releases sequestered E2F
• E2F- TF that drives cells from G1 to S phase

Question 7

simplified cell proliferation cascade

Answer 7

Myc increases CDK which phosphorylates Rb which releases E2F which drives cells from G1 to S phase

Question 8

E2F drives expression of what?

Answer 8

Cyclin E and Cyclin A

these activate CDK2

CDK2 hyper-phosphorylates Rb (inactive)

which activates E2F

allow transition pass G1 checkpoint

Question 9

what does CDK need to be active?

Answer 9

Cyclin (cyclin-dependent kinase)

Question 10

CDK activation

Answer 10

partially via binding of cyclin

full requires CDK- activating kinase (CAK)

Question 11

CDK inhibition

Answer 11

inhibitors (WEE1/ P27) inhibit cyclin CDK complex

inactivates kinase activity

Question 12

CDK-acitvating kinase (CAK) and the T-Loop

Answer 12

Question 13

What cyclin and CDK are used in restriction point

Answer 13

Cyclin D with CDK 4/6

inhibited by CKI (WEE1/p27)

Question 14

S phase CDK and cyclin type

Answer 14

Cyclin A with CDK2

Question 15

CDK and Cyclin in M phase/G2 cp

Answer 15

Cyclin A/B with CDK1

Question 16

What does WEE1 do in regulating CDK activity

What reverses it?

Answer 16

Question 17

What are the CDK inhibitory proteins?

Answer 17

P27 chich binds to both Cdk and cyclin

regulates early in cell cycle events (RP and G1 CP)

Question 18

how is cyclin regulated

Answer 18

cyclin turnover is regulated by signal-dependent protein degradation

Metaphase to Anaphase triggered by cyclin turnover

regulator (APC/C) cyclosome

which is a ubiquitin ligase family of enzymes

Question 19

what happens in order to move into anaphase in the cell cycle?

Answer 19

Cyclin-S and Cylin-M must be down regulated

APC/C activated by Cdc20 (binding)

APC/C poly ubiquitinates S and M cyclin

which go to proteosome destruction

no cyclins=inactive Cdk (dephosph)

Question 20

What are the ubiquitylation enzymes in APC/C regulation

Answer 20

E1 and E2

Question 21

P53 and the cell cycle

Answer 21

Question 22

P21 and the cell cylce

Answer 22

it is a cyclin-dependent kinase inhibitor (CKI)

usually CDK2

can do all cyclin/CDK complexes

Question 23

extrinsic pathway (apoptosis)

Answer 23

Question 24

Intrinsic pathway (apoptosis)

Answer 24

Question 25

Caspase activation

Answer 25

first procaspase which is activated by protease cleavage form a large and small subunit (heterodime)

Question 26

BCL-2 family

Answer 26

Bax and Bak are pro-apoptotic while Bcl-2 and Bcl-XL are anti-apoptotic

Question 27

Role of Bax

Answer 27

Question 28

Apaf1 and its role in the intrinsic pathway

Answer 28

Question 29

Factors that increase expression P53 BAX and BAK

Answer 29

tBid (caspase-8 activates Bid to tBId) this is for BAX and BAK DNA damage for P53

Question 30

What inhibits free cytochome C?

Answer 30

BCL-2 BCL-XL

Question 31

What inhibits Apaf1 binding to cytochrome C?

Answer 31

BCL-2

Question 32

proto-oncogene vs oncogene

Answer 32

Question 33

Retinoblastoma role with cancer

Answer 33

it is a tumor suppressor sequester E2F and prevents to much cell division

Question 34

Hereditary retinoblastoma

Answer 34

mutation or deletion in one Rb1 if another mutation then no more sequester E2F (common tumors in eyes)

Question 35

sporadic retinoblastoma

Answer 35

non-hereditary needs both copies of Rb1 to be mutated

Question 36

metastasis suppressors

Answer 36

cell adhesion proteins (prevent tumor cells from dispersing block loss of contact inhibition inhibit tumor metastasis

Question 37

affect of mutation on early and late stages of cancer

Answer 37

Question 38

The different hallmarks of cancer

Answer 38

Question 39

Viral oncogenes

Answer 39

* virus infects host * viral genome integrates into host genome next to proto-oncogene * replicates with hosts proto-onco * proto-onc mutates to oncogene * infects normal cell making it tumor cell

Question 40

HPV

Answer 40

E6 binds p53 causes degredation E7 binds Rb causes E2F to be unbound

Question 41

Chemo types

Answer 41

Question 42

Herceptin

Answer 42

binds HER2 receptor which doesnt allow dimerization which leads to degredation or lysis (breast cancer)

Question 43

Gleevec

Answer 43

chronic myelogenous leukemia

Question 44

Erbitux

Answer 44

cetuximab binds ligand that binds EGFR receptor a TK blocks action glioblastoma

Question 45

HER2 to oncogene

Answer 45

Val switched to glutamine causes TK activity activated in absence of ligand Breast Cancer

Question 46

EGF receptor to oncogene

Answer 46

EGFRvIII after deletion TK activity is always active glioblastoma

Question 47

ABL and BCR

Answer 47

by them selves fine but the fuse it goes into nucleus and acts as TF and cell cylce increase Chronic Myelogenous leukemia