cell proliferation

Question 1

what is cell proliferation

Answer 1

the increase in cell number (needed for homeostasis)

Question 2

control of normal cell proliferation

Answer 2

• signal is sent from a mitogen (growth factor) to induce homeostasis

Question 3

why is the mitogenic signal needed?

Answer 3

• cells can’t divide unless they have passed the restriction point at the end of the G1 phase
• they can only divide if the signal has been sent, the cell is undamaged, and the environment is right for it to divide
• the mitogen signal allows to overcome the R point

Question 4

Mitogen Activated Protein Kinase (MAPK) signalling cascade

Answer 4

• intrasignalling cascade that works downstream from signalling receptor
• it’s needed to sustain phosphorylation

Question 5

types of MAPK

Answer 5

• ERK pathway - growth factor
• p38 pathway and JNK pathway - DNA damage, cytokines, osmotic stress activating inflammation or apoptosis
• they all have 3 proteins in a cascade

Question 6

stages of cell proliferation

Answer 6

1. mitogen binds to complementary receptor
2. receptor becomes phosphorylated
3. receptor activation leads to the activation of g proteins
4. activated g protein attracts the first protein of the signalling cascade to become activated
5. signal is relayed from one signal to another (via phosphorylation)
6. signal finally relayed to transcription factors to induce cellular response

Question 7

turning off mitogenic signal at start

Answer 7

• release of mitogen is mediated by proteinases e.g. metalloproteinases
• blocking the action of metalloproteinases, you can block the release of the mitogen
• done through downregulation of receptor

Question 8

turning off mitogenic signal - receptor

Answer 8

• after receptor is phosphorylated, they are targeted for degradation
• they are tagged with ubiquitin which means they are delivered to the endosome where they fuse to the lysosome
• degraded so that no signal can be sent

Question 9

how does p53 act as a tumour suppressor

Answer 9

1. when cells sense DNA damage, kinases acting as sensors cause the phosphorylation of p53
2. phosphorylation of p53 prevents Mdm2 binding to p53 and hence blocks its degradation
3. p53 levels accumulate and co-ordinates the required response

Question 10

turn over of p53

Answer 10

• p53 is continuously synthesised and destroyed
• Mdm2 binds to p53 tagging it for degradation by the proteasome

Question 11

what are cdks

Answer 11

cyclin dependent kinases
- regulators at control points in cell progression of cell cycle

Question 12

how cdks work

Answer 12

• bound to respective cyclins they act on proteins
• they are kept at a constant level and are inactive
• need to be bound to cyclin to be activated
• when active they phosphorylate its substrate

Question 13

what is the function of the R point?

Answer 13

• first r point at the G1 phase halts the cell cycle
• means the cell can’t progress until appropriate level of mitogenic signal and optimum conditions are met

Question 14

mitogenic signals stimulating hyperphosphorylation of Rb

Answer 14

1. mitogen signalling activate transcription factors
2. transcription factors bind to DNA and codes for cyclin D mRNA
3. cyclin D mRNA is translated to produce cyclin D
4. cyclin D-binds and activates Cdk4/6
5. Cdk4/6 phosphorylates Rb which inactivates Rb and causes it to release its inhibition on E2f
6. E2f is now active and induces gene expression of cyclin E and other cyclins

Question 15

how can a cell pass the R point

Answer 15

cells need inactive Rb (retinoblastoma protein) and free E2f

Question 16

what do Cdk inhibitors do?

Answer 16

• bind to cyclin Cdk complexes to block action, so block cell cycle progression
• prevent passage of R point

Question 17

s phase

Answer 17

• DNA replicated
• synthesize chromatin proteins for packaging copied DNA into chromosmes

Question 18

g2 phase

Answer 18

delay the commitment of entering mitosis
- grows in size and checks DNA is faultless

Question 19

prophase and prometaphase

Answer 19

• cyclin B-Cdk1 phosphorylates proteins
• condensing of DNA
• formation of mitotic spindles
• breakdown of nuclear envelope
• preparation for chromosome segregation

Question 20

metaphase

Answer 20

• chromosomes move to the poles
• spindle assembly checkpoints (SAC)
• unattached kinetochores to the spindle is detected by SAC (can’t entre anaphase)

Question 21

anaphase and telophase

Answer 21

• chromatids are connected by cohesion proteins
• cyclin B-Cdk1 tiggers the breakdown of cohesions
• separation of chromatids need activation of anaphase promoting complex to destroy the connection
• deactivation of cyclin B-Cdk1 results in spindle disassembly and reformation of nuclear envelope

Question 22

what is necrosis

Answer 22

cell death due to injury or exposure to toxic chemicals

Question 23

what is apoptosis

Answer 23

programmed cell death

Question 24

what is caspases

Answer 24

proteases which cleave other proteins

Question 25

stages of caspases

Answer 25

1. caspases cleaves proteins of the cytoskeleton - bulging out of the membrane
2. caspases cleave proteins of the nuclear envelope causing the nucleases to breakdown
3. caspases activate nuclease which cut DNA into fragments
4. cell breaks into several apoptotic bodies
5. apoptotic bodies are cleared by macrophages through phagocytosis

Question 26

intrinsic pathway of cell death

Answer 26

1. DNA damage - P53 activated
2. expression of pyroptotic protein
3. protein leads to the release of cytochrome C from the mitochondria
   - signal of DNA damage comes from within the cell

Question 27

extrinsic pathway of cell death

Answer 27

• death receptor and death ligand