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WEEK 9 SEM 4 > Cellular Growth Regulation > Flashcards

Cellular Growth Regulation Flashcards

1
Q

What is hyperplasia?

A

increase in number of cells

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2
Q

What is hypertrophy?

A

increase in size of cells

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3
Q

How is growth of cells divided into?

A

growth of population of cells
growth at cellular level
loss of cells by programmed cell death (apoptosis)

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4
Q

What are the 4 phases of the cell cycle?

A

M
G1
S
G2

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5
Q

wHEN IS APOPTOSIS NEEDED?

A

NORMAL DEVELOPMENT- EMBRYO, METAMORPHSOSIS

DNA DAMAGE

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6
Q

What are growth factors, cytokeines and interleukins?

A

proteins that proliferate (MITOGENS) and maintain survival

e.g. epidermal growth factor (EGF), fibroblast growth factor (FGF), interleukins (IL2 and IL4), nerve growth factor (NGF)−there are other examples as well like platelet derived growth factor (PDGF) and insulin like growth factor (IGF1) which is the main effector of growth hormone

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7
Q

What stimulates differentiation and inhibits proliferation?

A

TGFB

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8
Q

What causes apoptosis of cells?

A

TNF alpha

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9
Q

What is paracrine?

A

produce GF locally, act on different cell in neighbourhood

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10
Q

What is autocrine?

A

produce GF, act on self

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11
Q

What is endocrine?

A

produce GF, enter circulation, act away from site

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12
Q

Explain the cell population growth graph:

A
  1. no increase in cell number as these cells are not dividing
  2. then growth factor is added to the cells, and the cells begin to proliferate
  3. when growth factor is removed, the cells stop dividing and thus there then a constant number of cells
  4. GF added again= the cells begin to divide and increase in number until a growth inhibitor is added to it, which stops cell division
  5. finally, a death signal is given to the cells, and all the cells apoptose and the cell numbers decrease rapidly
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13
Q

What happens in the M phase of the cell cycle?

A

mitosis= chromosomes form, align, split into 2 daughter cells

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14
Q

What happens to the 2 daughter cells?

A

both can enter

normally 1 enters and the other goes into quiescent phase

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15
Q

What happens to quiescent cells?

A

rest until given signal to divide/differentiate
OR
enter terminal differentiation and reaches post mitotic phase- this cell then dies (apoptosis)

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16
Q

What happens in interphase?

A

G1, S, G2

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17
Q

What happens in G1 phase?

A

it is 2N here
growth= size, nutrients
produce ATP
only place responsive to GF

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18
Q

What happens in the S phase?

A

synthesis
replicate
become 4N
add thymidine

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19
Q

What happens in the G2 phase?

A

grow in size

make sure all fine

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20
Q

What is shown in slow dividing cells?

A

most cluster in G1

equal in S and G2

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21
Q

What is shown in fast dividing cells?

A

most in G1 and G2/M phase

some cells in S phase

22
Q

What are the phases of mitosis?

A 
interphase (before mitosis)
prophase
prometaphase
metaphase
anaphase
telophase
cytokinesis
23
Q

What happens in prophase?

A

Nucleus becomes less definite
Microtubular spindle apparatus assembles
Centrioles (yellow) migrate to poles

24
Q

What happens in prometaphase?

A

Nuclear membrane breaks down

Kinetochores attach to spindle in nuclear region

25
Q

What happens in metaphase?

A

Chromosomes align in equatorial plane

26
Q

What happens in anaphase?

A

Chromatids separate and migrate to opposite poles

27
Q

What happens in telophase?

A

Daughter nuclei form

28
Q

What happens in cytokinesis?

A

Division of cytoplasm

Chromosomes decondense

29
Q

What are S phase active drugs?

A

5-fluorouracil- thymadine analogue

bromodeoxyuridine- thymadine analogue

30
Q

What does 5-fluorouracil do?

A

blocks enzyme thymidylate synthase
blocks one nucleotide
so DNA synthesis cant happen

31
Q

What does bromodeoxyuridine do?

A
  • gets incorporated into DNA as it gets synthesised

- detected by antibodies to identify cells that have passed through the S-phase

32
Q

What is an M phase active drug?

A

colchicine
vinca alkaloids
paclitaxel

33
Q

What does colchicine do?

A

it stabilizes free tubulin
SO preventing many tubulin molecules from forming microtubules
stopped the cell cycle in mitosis

34
Q

What is colchicine used in?

A

karyotype analysis

35
Q

What does paclitaxel do?

A

opposite of colchicine and stabilizes and promotes microtubule formation, preventing depolymerization

36
Q

What can 5-fluorouracil, paclitaxel, the vinca alkaloids and tamoxifen be used for?

A

cancer treatment

37
Q

Where are the checkpoints of the cell cycle?

A
  1. restriction point= after G1, Before S
    checks DNA damage, right size, enough nutrients?
  2. before mitosis
    check DNA damage and right replication
  3. during mitosis
    when chromosomes aligned on spindle
    check right number of chromosomes
38
Q

What does cyclin do?

A

regulates cyclin dependent kinase

needs to bind together for kinase to work (to phosphorylate)

39
Q

How is cyclin- cyclin dependent kinase activity regulated?

A

have to have CDK, cyclin and substrate protein
depends on post translational modifications = CDK can be active, inhibited or destroyed
Cyclical synthesis (gene expression) and destruction (by proteasome).
Dephosphorylation
Binding of cyclin-dependent kinase inhibitors

40
Q

What does retinoblastoma protein bind to?

A

transcription factor E2F

this stops protein getting into DNA

41
Q

What does Cyclin-CDK complex do to retinoblastoma?

A

bind to it
phosphorylates the protein
conformational shape= detach from E2F

42
Q

When E2F is free, what can it do?

A

free to bind to DNA
stimulates expression of more cyclin and CDK
stimulates transcription of DNA polymerase, thymidine kinase, PCNA etc (everything that is required to progress into the S phase)

43
Q

Where is RB with E2F found?

A

G1 phase of the cell cycle

44
Q

What inhibitis CDK activity?

A

CDK Inhibitory Protein/Kinase Inhibitory Protein (CIP/KIP) family (now called CDKN1)

inhibitor of kinase 4 (INK4)

45
Q

What does CDK Inhibitory Protein/Kinase Inhibitory Protein (CIP/KIP) family (now called CDKN1) stimulated by?

A

stimulated weakly by TGFB and strongly by DNA damage
this molecule inhibits all types of CDK-cyclin complexes (G1, G2 and M)

these molecules are inhibited by G1 CDKs in order to allow activation of CDKs in later stages of the cell cycle

46
Q

What is INK4 stimulated by and what does it do?

A

Expression stimulated by TGF beta

Specifically inhibit G1 CDKs (e.g. CDK4 the kinase activated by growth factors)

47
Q

What happens in the control of the cell cycle?

A
  1. initially in the early G1 phase, some early genes are activated−these early genes do not activate cyclin D and other genes immediately
  2. these early genes will result in the activation of other transcription factors which will later on activate delayed genes
  3. eventually the delayed genes will get activated which will lead to the expression of cyclin D and E
  4. this will lead to the activation of E2F,which will act as a transcription factor and activate genes
  5. the E2F responsive genes will be activated thus leading to activation of cyclin A
  6. after this, all the genes will be down regulated as they are not required during the G2 phase
48
Q

When are different cyclins active in the cell cycle?

A

cyclin D and E are active during the G1 and S phases

cyclin A is active during the G2 phase

cyclin B is active during the M phase

49
Q

What happens if damaged DNA is detected?

A
  1. cell expresses CDK inhibitors
  2. cell stops dividing and arrests in cycle
  3. now try repair DNA
  4. if repaired= go back in cycle
  5. if damage too bad= cell death
    cell death activate= BCL2= caspases
50
Q

What is TP53?

A

NORMAL CELL= protein TP53 always made and degraded (by proteasome)

when DNA damage detected= TP53 activates kinase

kinase can phosphorylate TP53

51
Q

What happens when TP53 is phosphorylated?

A

due to the phosphorylation, the TP53 is no longer destroyed by proteasomes

52
Q

What does TP53 do?

A

transcription factor
activates genes involved in DNA repair eg excision repair
if repair fails to occur, the TP53 can also activate genes that are involved in programmed cell death (apoptosis)

WEEK 9 SEM 4 (9 decks)

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