lecture 12- Cell cycle and cancer 2

Question 1

which out of cyclin and CDKs are always present in cells

Answer 1

CDKs

Question 2

what do Cyclin/CDK complexes promote through the cell cycle

Answer 2

progression

Question 3

how do cyclin/DK complexes promote progression

Answer 3

send signals to proteins to move cells through

Question 4

where are CDKs located in the cell

Answer 4

nucleus

Question 5

describe the steps of CDK activation

Answer 5

1)cyclin binds
2)phosphorylation
3)removal of inhib protein
4)dephosphorylation
5)then its active

Question 6

describe the steps of CDK inactivation

Answer 6

1)phosphorylation of cyclin
2)ubiquination of cyclin
3)degregation of cyclin

Question 7

why does ubiquination allow for the cell cycle to progress in one direction

Answer 7

it is a quick process which removes cyclins

Question 8

which cyclins/CDKs are present in each stage of the cell cycle

Answer 8

G1= CDK4/6 and cyclin D
just after R = CDK2 and cyclin E
S= CDK2 and cyclin A
G2 = CDK1 and cyclin A
M= CDK1 and cyclin B

Question 9

what is the inhibitor of CDK4/6

Answer 9

INK4

Question 10

what are the inhibitors of CDK1/2

Answer 10

Kip and cip

Question 11

what 2 things is cyclin d controlled by

Answer 11

GFs
integrin mediated ECM attachment

Question 12

what do mutations in cyclin D1 lead to

Answer 12

constituative nuclear localisation and impaired degregation

Question 13

what does ectopic expression of cyclin D1 in pancreatic cells lead to

Answer 13

increased cell proliferation
increased anchorage independant growth
decrease in chemosensitivity

Question 14

How doe shRNA reduce cyclin D1 and how has this been shown

Answer 14

it depletes its mRNA

when D1shRNA cells were added to a tumour from a mouse, the size decreased

Question 15

why is it better to use a virus to inject cyclin D1 shRNA into mice

Answer 15

means you dont have to take out the tumour from the body

Question 16

why is induced apoptosis a result of cyclin D1 shRNA expression

Answer 16

due to G1 arrest in absence of cyclin D

Question 17

how has cyclin D been shown to have prognostic role in gastric cancers

Answer 17

overexpression correlates with lower survival

Question 18

Where is cyclin E located in the cell cycle

Answer 18

after R point

Question 19

describe cyclin Es involvement in ovarian cancer

Answer 19

overexpression promotes cell growth of primary tumours and loss of contact inhibition

due to increased mRNA and proteins

Question 20

which mutation causes ovarian cancer

Answer 20

p53

Question 21

what is loss of contact inhibition

Answer 21

when cells dont stop dividing when they touch eachother

Question 22

describe cyclin Es involvement in breast cancer

Answer 22

when the CLEAVED form of cyclin e is present, there is dysregulation and resistance to therapy = poor prognosis

Question 23

What does early stage TGF-b do

Answer 23

arrests growth

Question 24

what does late stage TGF-b do

Answer 24

contributes to tumour invasiveness

Question 25

describe the TGF-b pathway

Answer 25

1)ligand binds to type 2 receptor 2)recruits type 1 receptor and phosphorylates 3) R-SMAD phosphorylated 4) SMAD binds 5) R-SMAD and SMAD act as transcription factors

Question 26

How does TGF-b arrest growth

Answer 26

it increases levels of INK which inhibits cyclin D-CDK4/6 so cells cant reach R point it weakly induces CIP which inhibits CDK1/2

Question 27

how do the effects of TGF-b change when when DNA damage occurs

Answer 27

stronger induction of CIP to ensure cell doesnt go into S phase

Question 28

What do Gfs release to combat the affects of TGF-b

Answer 28

Akt

Question 29

what are the 2 downstream affects of Akt

Answer 29

1) phosphorylates KIP to prevent nuclear translocation 2) phosphorylates and moves CIP into cytoplasm inactivates both of them

Question 30

how to Akt and TGF-b link together

Answer 30

they antagonise eachother Akt increases cell growth TGF-b stops it

Question 31

what is TGF-beta in the same family as

Answer 31

BMP