cellular growth regulation Flashcards

1
Q

define hyperplasia

A

an increase in cell numbers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

define hypertrophy

A

an increase in cell size

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are the main stages of cell division

A

cell cycle stages (G1, S, G2 and M)

one stage outside of cell cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are restriction points (in cell cycle)

A

checkpoints at which a cell will exit the cell cycle if certain requirements to proceed to synthesis are not met

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is apoptosis

A

programmed cell death
coordinated method of cell dismantling - & eventually phagocytosis
occurs in response to DNA damage and viral infection.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

briefly, what do cytokines and interlukins do

A

some stimulate proliferation of cells and maintain their survival
some stimulating differentiation of cells and inhibit proliferation
some induce apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what do mitogens do

A

stimulate cell growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are the 3 broad classes of hormones

A
  1. p aracrine
  2. autocrine
  3. endocrine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what are paracrine hormones

A

hormones produced locally to stimulate proliferation of a different cell type (in nearby environment) that has the appopriate cell surface receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are autocrine hormones

A

hormones produced by a cell that also expresses the appropriate cell surface receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what are endocrine hormones

A

hormones released into circulation for distant effects e.g. IGF-1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what happens to cells in culture when you add growth factor

A

stimulate cell growth of the population

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what happens when you remove growth factor from cells in culture

A

population will undergo growth arrest as they require continuous stimulation to grow.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what happens when you add a growth inhibitor such as TGFb to cells in culture

A

cause growth arrest of cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what happens when you add TNFa to cells in culture

A

cause cell death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what are the phases of the cell cycle

A

Interphase is composed of G1 phase (cell growth), followed by S phase (DNA synthesis), followed by G2 phase (cell growth). At the end of interphase comes the mitotic phase, which is made up of mitosis and cytokinesis and leads to the formation of two daughter cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what happens during G1 of cell cycle

A

the cell grows physically larger, copies organelles, and makes the molecular building blocks it will need in later step

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what happens during S stage of cell cycle

A

ell synthesizes a complete copy of the DNA in its nucleus. It also duplicates a microtubule-organizing structure called the centrosome. The centrosomes help separate DNA during M phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what happens during G2 of cell cycle

A

he cell grows more, makes proteins and organelles, and begins to reorganize its contents in preparation for mitosis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what happens after interphase in cell cycle

A

cell can either come out of cell cycle - into G0. (cells undergo growth arrest)
or undergo mitosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what may cause cells in G0 to reenter cell cycle

A

at this phase cells are sensitive to growth factor.

exposure to GF = reenter cell cycle.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what is DNA content of the cell after S phase

A

4N

replicating its DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what is DNA content of the cell after dividing

A

2N

diploid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

how do we measure the stage of cell cycle

A

use a fluorescence activated cell sorter

this measures amount of flourescence in a cell based on how much DNA it has.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

how does a population of cells with a low rate of cell division present on cell sorting

A

most of cells in g1 phase

only few are in S or G2/M phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

how does a population of cells with a high rate of cell division present on cell sorting

A

much more of cells in s and G2/M phase

which explains why pop is growing a lot

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what does it mean when we say DNA is replicated semiconservatively

A

the daughter cells containing one parental strand and one new strand.

28
Q

in which direction is new DNA sythesised and by which enzyme

A

5’ to 3’ direction by DNA polymerase

29
Q

in which direction is DNA read

A

read in 3’ to 5’ direction

30
Q

what safegaurds does DNA have to guard against mutation

A

proof-reading function and mismatch repair system

31
Q

why do we have the formation of okazaki fragments

A

DNA polymerase only works in the 5’-3’ direction
so on laying down primar from replication fork:
one strand is able to be made continuously
other strand has to keep reinitiating sythesis of the strand by laying down new primers.

32
Q

what do we do with the okazaki fragments

A

is called the discontinuous strand.

the fragments have to be ligated together after removal of RNA primers

33
Q

what are the 5 stages of mitosis

A
  1. prophase
  2. prometaphase
  3. metaphase
  4. Anaphase
  5. telophase
34
Q

what happens in prophase

A
  • nuclear membrane breaks down (nucleus less definite)

- mitotubular spindle apparatus assembles with centrioles migrating to opposite poles of nucleus

35
Q

what happens in prometaphase

A
  • nuclear membrane completely breaks down

- kinetochores of chromosomes attach to spindle

36
Q

what happens in metaphase

A
  • chromosomes align in equatorial plane
37
Q

what happens in anaphase

A

sister chromatids separate and migrate to opposite poles of the cell

38
Q

what happens in telophase

A

Daughter nuclei start to form

39
Q

what happens in cytokinesis

A
  • Division of cytoplasm between cells

- Chromosomes decondense back to chromatin

40
Q

what effect does 5-flourouracil have on the cell cycle

A

5-fluorouracil (an analogue of thymidine) blocks thymidylate

41
Q

what effect does bromodeoxyuridine

A

analogue of thymidine
- incorporated into DNA
detected + detected by antibodies
detected by antibodies to identify cells that have passed through the S phase

42
Q

what effect does colchicine have on the cell cycle

A

stabilises free tubulin preventing microtubule polymerisation and this arrests the cell in mitosis
- used in karyotype analysis

43
Q

what effect does paclitaxel (Taxol) have on the cell cycle

A

stabilises microtubules preventing de-polymerisation, inhibiting their function

44
Q

where are the three restriction points of the cell cycle

A

1 - late G1
2 - just before entry into meiosis
3 - at the point where chromosomes are aligned on equatorial plate spindle

45
Q

what does the late G1 checkpoint asess

A

Is DNA damaged
what is the cell size
has it grown adequately
are their sufficient metabolite/nutrient stores

46
Q

what does the post entry into meiosis checkpoint assess

A

Is the DNA completely replicated

Is it damaged

47
Q

what does the checkpoint at the point where chromosomes are aligned on the equatorial plate spindle assess

A

are all the chromosomes aligned

48
Q

at which point of cell cycle are cells most responsive to growth factors

A

g1

49
Q

at what stage are cells in a tissue regulated

A

G1

50
Q

what are kinases

A

enzymes that phosphorylate other proteins

51
Q

what is the active kinase made up of

A

1 - CDK calatytic unit

2 - cyclin regulatory unit

52
Q

what is a cyclin dependent kinase

A

requires the binding of cyclin to phosphorylate

involved in regulating the cell cycle

53
Q

where does cyclin bind on the cyclin dependent kinase

A

cyclin binds to CDK to form the active cyclin CDK complex

is then able to phosphorylate

54
Q

how do we regulate the cyclin-CDK activity

A

1 - through cyclin synthesis + degredation (via proteosome)
2 - post-translational modification by phosphorylation. site of phosphorylation = activation/inhibition or destruction
3 - dephosphorylation of the complex
4 - binding of cyclin dependent kinase inhibitors

55
Q

what is the role of retinoblastoma in inhibiting progression through cell cycle

A

RB = key substrate of G1 & G1/S CDK.
RB is usually unphosphorylated. when in this state, it binds to E2F. bound so E2F cannot stimulate S-phase proteie expression so cell cannot progress into S phase.

56
Q

role of CDK + retinoblastoma in progression into S phase.

A

When CDK present, it phosphorylates E2K so RB released.
E2K -> nucleus. binds promoter regions of cyclin and S-phase proteins.
-> Production of these S phase proteins allows for DNA replication of the S phase to start

57
Q

what are some cyclin dependent kinase inhibitors

A

two families of CDKIs
1 - CDK Inhibitory Protein/Kinase inhibitory protein family
2 - Inhibitor of Kinase 4 family

58
Q

why do we need CDK inhibitors in the body

A

Loss of some of these CKIs can lead to cancer as no brake on progression.

59
Q

how do CDK Inhibitory Protein/Kinase inhibitory protein family work

A
  • protein inhibitors act on both sides of catalytic unit and cyclin subunit
  • can inhibit all other CDK-cyclin complexes (late G1, G2 and M) so can work throughout the cell cycle
60
Q

what stimulates the expression of

CDK Inhibitory Protein/Kinase inhibitory protein family

A

weakly by TGFb (inhibitor of cell growth) and strongly by DNA damage (by TP53)

61
Q

what stimulates Inhibitor of Kinase 4 family

A

stimulated strongly by TGFb

62
Q

what does Inhibitor of Kinase 4 family inhibit

A

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

63
Q

how do growth factors induce cyclin expression

A

1.GF binds to cell surface receptor, triggering signal transduction
2.1st wave of transcription/translation products go back to nucleus. stimulate delayed gene expression
Initial proteins are cyclin D and CDK proteins & E2F
3.Cyclins stimulate further expression of cyclin
4.E2F inactive, as is bound to unphosphorylated RB
5.Cyclin-CDK complex increase. More phosphorylation of RB .’. E2F release
6.Expression of E2F responsive genes that allow progression into S phase

64
Q

what happens if DNA damage is detected at a restriction site?

A
  1. CDKI arrest the cell cycle
  2. cell attempts to repair DNA damage by nucleotide excision enzymes or mismatch repair system
  3. if repair is excessive/irreparable, triggers apoptosis (via BCL2 family & caspases)
65
Q

what is p53

A

is a transcription factor.

exists transiently in the cell and degraded by enzymes

66
Q

role of p53 in respnse to DNA damage

A

if DNA damage is detected:
P53 phosphorylated = more stable
1. stimulates expression of CDKI (.’. arrests cell cycle)
2. P53 stimulates expression of DNA repair proteins (if repaired cell -> cell cycle)
3. if repair not possible, p53 stimulates apoptosis