Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

HemOnc Week 2 > LM 7.1: Cell Cycle Regulation > Flashcards

LM 7.1: Cell Cycle Regulation Flashcards

1
Q

what is positive regulation of the cell cycle?

A

promotes cell cycle progression

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

what are some external inducers of the cell cycle?

A
  • growth factors
  • mitogens
  • mechanical forces
  • signal transduction pathways

these all feed into the cell cycle in various ways to facilitate proliferation

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

what are some cell cycle regulators that positively regulate the cell cycle?

A
  • cyclins
  • cyclin dependent kinases (CDKs)

cell cycle regulators that positively affect cell cycle progression and promote proliferation

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

what is negative regulation of the cell cycle?

A

stops or pauses cell cycle progression

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

what are cell cycle checkpoints?

A

mechanisms that ensure quality control of the cell cycle by allowing pauses before professing to the next step

ensures that environmental conditions are factorable for division, that earlier steps have been completed and that the cell is ready to proceed

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

what is a restriction point in the cell cycle?

A

critical point when the cell commits to cell cycle progression

at this point, external inducers like growth factors are no longer necessary

these are points for negative regulation of the cell cycle and limit proliferation

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

what are some cell cycle regulators that negatively regulate the cell cycle?

A

retinoblastoma protein (RB)

P53

cyclin dependent kinase inhibitors (CDKIs)

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

what things can induce the cell cycle?

A
  • stretching of smooth muscle
  • cell injury
  • cell death
  • growth factors
  • mitogen

they all stimulate signal transduction pathways that lead to cell cycle progress

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what are the phases of the cell cycle?

A
  1. interphase: G1, S, G2
  2. mitosis
  3. cytokinesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what happens during the G1 phase of interphase?

A

cellular contents, excluding the chromosomes are duplicated

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

what happens during the S phase of interphase?

A

each of the 46 chromosomes is duplicated by the cell

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

what happens during the G2 phase of interphase?

A

the cell double checks the duplicated chromosomes for error and makes any repairs

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

how do CDKs work?

A

the cell cycle is positively regulated by kinases

kinases are composed of a catalytic subunit called the cyclin dependent kinase (CDK)

CDKs are only active when they dimerize with a regulatory subunit called cyclin

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

what type of kinase are CDKs?

A

serine/threonine protein kinases

CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases

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

what are cyclins?

A

they bind to CDKs to regulate their activity

CDKs are dependent on cyclins for their activity

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

what happens when cyclin binds to CDK?

A

CDK isn’t active unless it’s bound to cyclin

when cyclin binds, it causes a conformation change that exposes the T-loop in the ATP binding domain of the CDK which makes CDK partially active

then CDK-activating kinase (CAK) phosphorylates certain key AA in the T-loop of CDK and makes the cyclin-CDK complex fully active

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

what are the four categories of cyclin-CDK complexes?

A

G1-CDK

G1/S-CDK

S-CDK

M-CDK

they are all serine-threonine protein kinases that function at the G1, G1/S, S and M phase of the cell cycle, respectively

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

what do cyclin-CDK complexes do?

A

each complex is compared of a regulatory cyclin subunit and a catalytic CDK subunit

the cyclin-CDK complex promotes cell cycle progression by phosphorylating serine-threonine residues on target proteins

some of the target proteins are RB, histone H1, and lamins

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

what are some of the target proteins of cyclin-CDK complexes?

A

RB, histone H1, and lamins

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

what does the G1-CDK complex do?

A

it functions early in G1 to promote progression through the restriction point

the restriction point is the point in G1 when the cell commits to proceeding to S phase

once this point is passed, the cell will continue its progress even if stimulatory signals from the environment are removed

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

which cyclins and CDKs make up the G1-CDK complex?

A

CDK 4/6

cyclin D

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

what does the G1/S-CDK complex do?

A

it’s important for progressing through the restriction point

23
Q

which cyclins and CDKs make up the G1/S-CDK complex?

A

CDK 2

cyclin E

24
Q

what does the S-CDK complex do?

A

upon entry into S phase, the S-CDK complex takes over and promotes progress through S phase to G2

25
Q

which cyclins and CDKs make up the S-CDK complex?

A

CDK 2

cyclin A

26
Q

what does the G2-CDK complex do?

A

it promotes progress through G2 to m PHASE

27
Q

which cyclins and CDKs make up the G2-CDK complex?

A

CDK1

cyclin A

28
Q

what does the M-CDK complex do?

A

it promotes mitosis, giving rise to 2 daughter cells

29
Q

which cyclins and CDKs make up the M-CDK complex?

A

CDK 1

cyclin B

30
Q

what happens to cyclin levels during the cell cycle?

A

they oscillate!

CDK levels are constant during the cell cycle but the activity of these kinases fluctuates due to oscillations in the levels of the cyclin subunit

for example, the G1-CDK complex is made up of CDK 4/6 and cyclin D so cyclin D accumulates during G1 which activates its respective CDK, CDK 4/6 –> this allows the cell to progress through G1

progressing through G1 phase triggers a rise in cyclin E which together with its respective CDK allows progress through the restriction point into S phase

cyclin D and cyclin E levels decrease as cyclin A levels rise –> cyclin A along with its respective CDK allows the cell to progress through S phase and into G2

once G2 is complete, cyclin A levels decrease and cyclin B levels increase which drives progress through mitosis

at the end of mitosis, cyclin B is degraded which allows the cell to exit mitosis and begin a new cycle

31
Q

how do cyclin levels increase?

A

cyclins accumulate during the cell cycle through the process of transcription

E2F proteins bind to the promoters of cyclin genes and activate expression

32
Q

how do cyclin levels decrease?

A

cyclin levels decrease by ubiquitination and proteolysis

APC or SCF ubiquitin ligase participate in the ubuquitination of cyclins and then the cyclin is targeted by proteosomes and degraded

33
Q

what is negative regulation of the cell cycle important for?

A

it’s critical for quality control so that the cell only progresses to the next phase upon completion of the prior stage

if there’s a malfunction that prevent completion of a process, signals are sent out to delay progression to the next step

there are sensors that detect completion of each step

34
Q

where are the checkpoints in the cell cycle? what happens at them?

A

G1 checkpoint checks for DNA damage

S checkpoint checks for incomplete replication

G2 checkpoint checks for DNA damage

M checkpoint that checks for unattached kinetochores

35
Q

where is the restriction point in the cell cycle?

A

the restriction point is in G1

36
Q

what happens at the restriction point?

A

it’s during the G1 phase and it commits the cell to replicating its DNA and ultimately dividing

37
Q

progression through the restriction point is negatively regulated by what?

A

retinoblastoma protein (RB)

RB is the gatekeeper of the restriction point and plays a critical role in negatively regulating proliferation

it’s a sensor of nutrient conditions

38
Q

what does RB do?

A

RB stops progression from the G1 to S phase = negatively regulates the cell cycle

transcription of S phase genes like cyclin A and E is activated by the E2F transcription factors - accumulation of cyclin E allows cell to progress through the restriction point and proceed to S phase

BUT if conditions aren’t favorable for proliferation, then RB binds to E2F and blocks transcription of both cyclin A and E as well as other genes required for DNA replication during S phase

turning off cyclin A and E transcription is the mechanism that RB uses to stop the cell cycle when mitogenic signals are lacking

39
Q

how do you turn off RB so you can pass the G1 restriction point and continue on into S phase?

A
  1. RB is turned off when the G1 cyclin, cyclin D, accumulates and activates its respective CDK, CDK 4/6
  2. the cyclin D-CDK 4/6 complex then phosphorylates RB which causes it to dissociate from E2F
  3. E2F can now activate transcription of cyclin A and cyclin E gene promoters
  4. the G1-S cyclin, cyclin E, accumulates and associated with CDK2 and the cyclin E-CDK2 complex further phosphorylates RB

this is a positive feedback loop that blocks RB’s ability to inhibit E2F and enhances the signal to progress into S phase because it allows E2F to transcribe genes required for DNA replication

40
Q

what do CDKIs do?

A

cyclin-CDK inhibitors = CDKI = negatively regulate the cell cycle

CDKIs bind to both the CDK and cyclin subunits, insert into the ATP-binding cite and distort the active site of the CDKs

some CDKIs can cause cyclins to dissociate from the CDK

41
Q

what are some examples of CDKIs?

A

p16

p21

p27

42
Q

which CDKIs inhibits the G2-CDK complex?

A

p27 and p21

43
Q

which CKDKI inhibits the M-CDK complex?

A

p27 and p21

44
Q

which CDKI inhibits the G1-CDK complex?

A

p27, p21, and p16

45
Q

which CDKI inhibits the G1/S-CDK complex?

A

p27 and p21

46
Q

which CDKI inhibits the S-CDK complex?

A

p27 and p21

47
Q

what does p16 do?

A

it’s CDKI that inactivates cyclin-CDK4 and cyclin-CDK6 complexes

48
Q

what is p53?

A

p53 is a transcription factor that negatively regulates the cell cycle by sensing DNA damage

it responds to DNA damage at the G1 checkpoint and promotes expression of genes that inhibit cell cycle progression

p53 specifically activates expression of CDKI p21

49
Q

how are p53 levels controlled?

A

normally, p53 levels are kept low through association with a ubiquitin ligase called HDM2 which targets p53 to the proteasome so that its broken down

50
Q

what is a proteasome?

A

a protein complex in cells containing proteases

it breaks down proteins that have been tagged by ubiquitin

51
Q

what activates p53?

A

DNA damage from radiation, DNA damaging agents or even from normal metabolism would result in the phosphorylation of p53

p53 phosphorylation allows p53 to dissociate from HDM2 and accumulate in the cell

52
Q

what happens when p53 is activated?

A

DNA damage results in phosphorylation of p53 which allows p53 to dissociate from HDM2 and accumulate in the cell

activated p53 then activates expression of many genes, including CDKI p21

increased p21 expression inhibits G1 progression by inhibiting the activities of cyclin D-CDK4/6 and cyclin E/CDK2 complexes

this allows the cell to arrest in G1 in order to repair the damaged DNA

53
Q

what are the 4 functional domains of the p53 protein?

A

p53 is a transcription factor with four functional domains

  1. an N-terminal transactivation domain
  2. a central sequence-specific DNA binding domain
  3. a domain for p53 tetramerization
  4. a C terminal regulatory region that has sites for post-translational modifications and protein-protein interactions

HemOnc Week 2 (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions