topic 10 (part 2)

Question 1

cancer

Answer 1

an abnormal growth of cells with tend to proliferate in an uncontrolled way and in some cases metastasize (spread)

Question 2

malignancy

Answer 2

the tumor property to invade nearby tissues and spread (metastasize) to other body parts

Question 3

carcinogenesis

Answer 3

activation of oncogenes and inactivation of tumor-suppressor genes

Question 4

stages of carcinogenesis

Answer 4

1. loss of a tumor-suppressor gene
2. small benign growth (polyp)
3. activation of an oncogene
4. loss of another tumor-suppressor gene
5. larger benign growth (adenoma)
6. loss of tumor-suppressor gene p53
7. malignant tumor

Question 5

cell cycle checkpoints

Answer 5

• control the transition from one phase of the cell cycle to the next
• ensure that certain processes have been completed (ex: DNA replication) before another phase starts

Question 6

3 important checkpoints

Answer 6

G1 checkpoint
G2 checkpoint
M checkpoint

Question 7

G1 checkpoint

Answer 7

• checks for the presence of growth factors?
• cell size is large enough to divide?
• controls transition from G1 to S phase

Question 8

G2 checkpoint

Answer 8

• checks if there is any DNA damage?
• controls transition from G2 to M phase

Question 9

M checkpoint

Answer 9

controls the transition through the stages of mitosis

• correct chromosome alignment in the mitotic spindle during metaphase?

Question 10

if DNA damage is detected at G1 and G2 checkpoints

Answer 10

cell cycle arrest

Question 11

if cells are unable to repair damage, this leads to

Answer 11

apoptosis

Question 12

most important checkpoint

Answer 12

G1 checkpoint

Question 13

cell cycle control is maintained by protein complexes which are composed of 2 subunits

Answer 13

1. cyclin (cyc) - the regulatory unit
2. cyclin dependent kinase (cdk) - the catalytic subunit

Question 14

kinases

Answer 14

enzymes that inactivate/activate other protein by phosphorylation

Question 15

concentration fluctuates in the cell

Answer 15

cyclins

Question 16

the active form of cdks (cyc-cdk) can?

Answer 16

phosphorylate various proteins and can lead to protein activation/inactivation

Question 17

the activity of cdks is regulated by

Answer 17

degradation of cyclins by the proteasome

Question 18

proteasome

Answer 18

giant protein complexes that bind to protein molecules (such as cyclins) and degrade them (proteolysis)

Question 19

why is tight regulation of cdks very important?

Answer 19

loss of cell cycle control can lead to unregulated cell proliferation (carcinogenesis)

Question 20

binding of cdks to different cyclins causes

Answer 20

phosphorylation of different substrates

Question 21

the signal that sends cells into mitosis was named

Answer 21

MPF (mitosis promoting factor)

Question 22

MPF

Answer 22

• first cdk to be discovered
• consists of a mitotic cyclin (A or B) and cdk-1
• induces the progression from G2 to M phase

Question 23

MPF induces the progression from G2 to M phase by

Answer 23

phosphorylation and inactivation of APC (anaphase promoting complex)

Question 24

APC (anaphase promoting complex)

Answer 24

an E3 ubiquitin ligase which inactivates mitotic cyclins (cyc-A or cyc-B) and hence MPF, during interphase

Question 25

proteolysis of mitotic cyclins at the end of mitosis causes

Answer 25

reduction of MPF activity

Question 26

MPF inactive, APC active

Answer 26

interphase

Question 27

MPF active, APC inactive

Answer 27

M phase (mitosis)

Question 28

role of MPF: cell cycle regulation

Answer 28

- chromosomal condensation - nuclear envelope degradation - mitotic spindle formation - chromosome migration to opposite poles - organelle reformation - cytokinesis

Question 29

cell cycle regulation during interphase

Answer 29

- mitogens - expression of early response genes - activation of G1 cyclin-cdk activity - transcription of genes for DNA synthesis

Question 30

expression of early response genes

Answer 30

- G1 cyclins and cdks (cyc-D, cyc-E, cdks 2,4,6) - transcription factors (c-fos, c-jun, E2F)

Question 31

if the mitogen is removed

Answer 31

- reduction in the cyclin-cdk levels - the cell does not pass through the restriction point R - the cell does not replicate

Question 32

what do tumor suppressor genes do?

Answer 32

produce proteins that inhibit cell division and prevent uncontrolled cel growth (cancer)

Question 33

two important tumor suppressor genes

Answer 33

RB1 and TP53

Question 34

what is p53?

Answer 34

a protein produced by TP53 gene that inhibits cdks

Question 35

what is Rb?

Answer 35

- retinoblastoma protein - produced by the protein RB1 and inhibits cell cycle

Question 36

what happens when E2F is inactive?

Answer 36

the cell cannot enter S phase

Question 37

how is Rb's activity regulated?

Answer 37

1. G1 phase: Rb dephosphorylation by PP-1 2. at the end of G!, cyc-cdks phosphorylate Rb 3. phosphorylated Rb cannot sequester E2F 4. E2F is released (activated), and cells enter S phase

Question 38

what are the activities of Rb and E2F during G1 and S phase?

Answer 38

- G1: Rb active, E2F inactive - S: Rb inactive, E2F active

Question 39

what is retinoblastoma?