Cell replication

Question 1

Different division rates of cells

Answer 1

Embryonic vs adult cells (early frog embryo cells - 30min)

Yeast cells (1.5-3)

Necessity for renewal (intestinal epithelial cells - 20h, hepatocytes 1 yr)

Question 2

What is the quiescent phase

Answer 2

Go -

Question 3

What are the characteristics of cells going past the checkpoints

Answer 3

Based on nutreints

Growth factors

Question 4

Why might the cell cycle pause

Answer 4

Undergoes DNA repair

Undergo apoptosis

Question 5

How do cells leave Go

Answer 5

Reponse to extracellular factors

Tyrosine receptors

Signal amplification

Signal integration/ modulation by other pathways

Ras/Raf/MEK/ERK

Question 6

What is the role of c-Myc

Answer 6

Growth factor Induces the expression of c-Myc

Promotes Go to G1

c-Myc is an oncogene

Question 7

What are cyclin dependent kinases

Answer 7

Phosphorylation and dephosphorylation

Forms serine/threonine/tyrosine

Present in proliferating ecll sbut only activate when a cyclin is bound

Question 8

Why is cyclin called cyclin

Answer 8

Production and degradation cyclic pattern

Question 9

How are c-myx and cyclin relates

Answer 9

Growth factor induce C-Myc

C-Myc induces expression of Cyclin D

Cyclin D binds to Cdk 4

Question 10

What are protein kinase cascades

Answer 10

One kinase phosphorylates another kinase which phosphorylates another kinase

Leads to: signal amplification, diversification, opportunity for regulation

Phosphorylation and dephosphorylation controls

Question 11

How are the cyclin-dependent kinases regulated

Answer 11

Interaction with cyclins

Phosphorylation

Question 12

What are examples of cyclins

Question 13

How are cyclins expressed

Answer 13

Transiently expressed at specific points in the cell cycle

Regulated at level of expression

Synthesised then degraded

Question 14

Stages of phosphorylation and desphosphorylation

Answer 14

Cyclin bindes to cdk

Protein kinases phosphorylate complex

Activating protein phosphatase removes inhibitory phosphate - becomes active cyclin-cdk complex

Question 15

Positive feedback of cell cycle

Answer 15

Question 16

Progression induction of Cdks through the cell cycle

Answer 16

Question 17

What is ubiquitylation of cyclin

Answer 17

Ubiquitin molecules stick onto cyclin

Cell machinery proteasome

Question 18

How do you regulate cyclins in the cell cycle

Answer 18

Cdks become active and stimulate synthesis of genes required for next pahse eg. cyclinD stimulates cyclin E

Gives direction and timing

Susceptible to degradation

Question 19

What is retinoblastoma

Answer 19

Molecular brake

Problem when retinoblastoma protein is missing or inactive

Tumour suppressor

Abundant in all nucleated cells

Question 20

Growth factor (mitogen signalling)

Answer 20

Drives cell proliferation

Question 21

What does Rb do

Answer 21

Acts as a brake on cell proliferation

Active RB portein binds to inactivated transcription regulated (E2F family)

E2F family turn on DNA polymerase and thymidine kinase - things needed for S phase

Question 22

How is the Rb activated

Answer 22

Phosphorylation by activation of intracellular signaling leads to the production of G1/S-Cdk complexes

Question 23

How do E2F members regulate expression

Answer 23

Question 24

What does p53 do

Answer 24

Arrests cells with damaged DNA in G1

Recognise breaks and activated portein kinases that phosphorylate p53, stabilizing and activating it

Question 25

How does active p53 induce p21

Answer 25

Question 26

What do p21 do

Answer 26

Poptent inhibitors of Cyclin-Cdk complex

Question 27

How does the herceptinantibody work

Answer 27

Block HER2 oncogenes

Question 28

What are types of tumour suppressors

Answer 28

Rb - loss of function mutations 80% of small cell lung cancer

p53 - loss of function mutations in 50% of human cancers