cell cycle, apoptosis and cancer

Question 1

S phase of cell cycle

Answer 1

synthesis, chromosome duplication

Question 2

M phase of cell cycle

Answer 2

Mitosis
- Chromosome
Duplication/Segregation
- Cytokinesis- Cell Division

Question 3

Go Phase

Answer 3

Poor nutrient/environmental condition
cells withdraw from the cell cycle
Also occurs following terminal differentiation in certain tissue types (e.g. brain
neurons, cardiac muscle, RBCs)

Question 4

interphase

Answer 4

(G1) = Gap 1 phase- RNA and protein synthesis needed for DNA replication
(S) Phase DNA synthesis
(G2) Gap 2 phase- DNA stability is checked

Question 5

Restriction point cell cycle

Answer 5

between G1 and S phase

-if growth factors are limited

Question 6

what are checkpoints in cell cycle?

Answer 6

1) restriction point
2) G1 checkpoint
3) metaphase checkpoint
4) G2 checkpoint

Question 7

G1 checkpoint

Answer 7

• Timing is similar to restriction point

- Occurs in response to DNA damage

Question 8

G2 checkpoint

Answer 8

-Verify complete genomic duplication

Question 9

metaphase checkpoint

Answer 9

-Ensures chromosomes attached to mitotic spindle

Question 10

how does RB act as a tumor suppressor?

Answer 10

sequester E2F

Question 11

What does entry from S phase to G1 require?

Answer 11

E2F to be active

Question 12

what phosphorylates RB to make it inactive and activated E2F?

Answer 12

CDK2

Question 13

what do cyclins require to be active?

Answer 13

• cyclins

- CAK (t loop in cave site)

Question 14

what expression rises and falls throughout the cell cycle?

Answer 14

Cyclin expression

-causes kinase activity to rise and fall

Question 15

CDK4 and CDK6

Answer 15

helps the passage of cells through the restriction point in late G1 phase

Question 16

Wee1 Kinase

Answer 16

inhibits Cdk activity by phosphorylating the roof site

Question 17

Cdc25

Answer 17

dephosphorylates roof site to increase CDK activity

Question 18

CKI (p27)

Answer 18

bind to Cdk and cyclin

-inhibits (G1 to S transition)

Question 19

Metaphase to anaphase requires which key regulator?

Answer 19

APC/C (cyclosome)

-member of ubiquitin ligase family of enzymes

Question 20

what does APC/C do?

Answer 20

-activated by Cdc20
addition of polyubiqutin to S and M cyclin complexes
-cyclins targeted for destruction by proteasome
-inactivates CdKs

Question 21

p53

Answer 21

• activated by phosphorylation
  -leads to increased transcription of CKI (P21)
  p21= cell cycle arrest

Question 22

what keeps p53 inactive?

Answer 22

E3 ubiquitin ligase (MDM2)

Question 23

p21

Answer 23

• is a CKI
• primarily associated with inhibiting CDK2
• major target of P53

Question 24

extrinsic (death receptor) pathway

Answer 24

• Fas ligand activates FADD
• Procaspase 8 to caspase 8
• activates caspase 3,6,7
• apoptosis

Question 25

intrinsic (mitochondrial pathway)

Answer 25

- Caspase 8 active - release of cyt C from Mito - APAF-1 forms apoptosome - activates Caspase 9 - activates caspase 3,6,7 - apoptosis

Question 26

what are the initiators caspases

Answer 26

Caspase-8 and Caspase-9

Question 27

what are the executioner caspases

Answer 27

caspase 3

Question 28

what stimulates the intrinsic apoptotic pathway?

Answer 28

- p53 - BAX - BAK

Question 29

what inhibits the intrinsic apoptotic pathway

Answer 29

BCL2 | BCL XL

Question 30

how does proto oncogene become an oncogene

Answer 30

gain of function mutation

Question 31

Her2 Receptor to oncogene

Answer 31

becomes oncogene after Val replaced with Gln - RTK activity always active - becomes NEU - breast cancer - Gain of Function

Question 32

EGF receptor to oncogene

Answer 32

deletion changes to EGFRvIII RTK activity always active -Glioblastoma

Question 33

ABL and BCR gene to oncogene

Answer 33

translocation creates BCR-ABL gene - acts as TF - Chronic myelogenous leukemia (CML)

Question 34

hereditary form of retinoblastoma

Answer 34

- mutation/deletion in one copy of RB1 (heterozygous) - second hit required for cancer - loss of heterozygosity

Question 35

sporadic form of retinoblastoma

Answer 35

- non hereditary - cancerous cell have both copies of RB1 mutated - rare - requires 2 indp. mutations

Question 36

loss of function mutations in tumor suppressor genes

Answer 36

- p53 - RB - APC - DCC - BRCA1/BRCA2 - NF-1

Question 37

Metastasis Suppressors

Answer 37

Cell adhesion proteins - Prevent tumor cells from dispersing - Block loss of contact inhibition - Inhibit tumor metastasis

Question 38

Hallmarks of cancer cells

Answer 38

1) self sufficiency in growth signals 2) evading growth suppressors 3) activating invasion and metastasis 4) enabling replicative immortality 5) inducible angiogenesis 6) resisting cell death

Question 39

ex of a viral oncogene

Answer 39

HPV

Question 40

Viral oncogenes

Answer 40

proto oncogene infected by virus- viral genome integrates - virus replicates - protooncogene mutated to oncogene - can infect other cells

Question 41

alkylating agents

Answer 41

- block DNA replication | - all phases of cell cycle

Question 42

antimetabolites

Answer 42

- inhibit enzymes involved in DNA synthesis | - S phase

Question 43

Topoisomerase II inhibitors

Answer 43

- S phase G2 phase M phase

Question 44

mitotic inhibitors

Answer 44

- arrest cells in mitosis during metaphase | - M phase

Question 45

cytotoxic antibiotics

Answer 45

- intercalate between bases in DNA to inhibit DNA synthesis | - S and G2 phase

Question 46

topoisomerase I inhibitor

Answer 46

- S phase

Question 47

Herceptin

Answer 47

-targets HER2 receptor or NEU

Question 48

Gleevec

Answer 48

- works with BCR/ABL enzyme and prevents phosphorylation of target protein - used in CML