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2.1 Cell and Molecular Biology > Carla - Regulation of the Cell Cycle > Flashcards

Carla - Regulation of the Cell Cycle Flashcards

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1
Q

What needs to be controlled?
(4)

A

The length of time the cell spends in each phase

The initiation of events in correct order

Ensure each event is only triggered once per cycle

A binary switch to trigger events completely and irreversibly - either on or off

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2
Q

How are checkpoints controlled?

A

There is negative control of checkpoints

The cell checks what hasn’t been done -> no positive signals stimulate

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3
Q

Why do we need checkpoints?

A

Cells would never replicate

Cells would never stop replicating

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4
Q

What three regulators are important at the checkpoints?

A

Cyclins

CDKs -> cyclin dependant kinases

Tumour suppressors

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5
Q

What are cyclins?
(3)

A

Core cell cycle regulators

Group of related proteins

Four basic types found in humans

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6
Q

What are the four basic types of cyclins?

A

G1 cyclins

G1/S cyclins

S cyclins

M cyclins

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7
Q

When do C1 cyclins peak?

A

Doesn’t really peak

Begins to raise at G1 phase and decreases back down by the M phase

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8
Q

When do G1/S cyclins peak?

A

The beginning of the S phase

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9
Q

When do S cyclins peak?

A

The G2 phase

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10
Q

When do M cyclins peak?

A

The M phase

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11
Q

How do cyclins work?
(2)

A

They drive the cell cycle forward by activating or inactivating target proteins inside the cell

They cannot work alone - they must be coupled with CDKs

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12
Q

What are kinases?

A

Enzymes that are able to phosphorylate

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13
Q

What does CDK stand for?

A

Cyclin dependent kinases

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14
Q

What are CDKs?
(3)

A

Large family of serine/threonine kinases

Dependent on cyclins

Different types are restricted to specific stages of the cell cycle

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15
Q

List four CDKs

A

CDK4
CDK6
CDK2
CDK1

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16
Q

What do CDK4 and CDK6 do?

A

They regulate the G1 stage

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17
Q

What does CDK2 do?

A

Regulates the transition of G1 to s phase

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18
Q

What does CDK1 do?

A

Regulates G2 and mitosis

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19
Q

Give four examples of cyclins

A

Cyclin D, E, A and B

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20
Q

What type of cyclin is cyclin D?

A

G1 cyclin

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21
Q

What type of cyclin is cyclin E?

A

S-phase cyclin

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22
Q

What type of cyclin is cyclin A?

A

S-phase and mitotic cyclin

23
Q

What type of cyclin is cyclin B?

A

Mitotic cyclin

24
Q

Write a note on cyclin D
(5)

A

Expression is induced by stimulation by growth factor, amino acids, hormones and oncogenes such as Ras

Partners with CDK4 and CDK6 in early to mid G1 phase

Phosphorylates and inactivates the cell inhibitory function of the retinoblastoma protein in cooperation with cyclin E/CDK2

Known to modulate local chromatin structure and transcription of genes involved in proliferation and differentiation through CDK-independent association with histone acetylases and deacetylases

Amplification/overexpression is seen in many cancers -> 45% of mammary cancers (mammary oncogene)

25
Q

What induces the expression of Cyclin D1?

A

Expression is induced by stimulation by growth factor, amino acids, hormones and oncogenes such as Ras

26
Q

What can Cyclin D partner with?

When does cyclin partner with these?

A

Partners with CDK4 and CDK6 in early to mid G1 phase

27
Q

What does cyclin D partnered with CDK4 and CDK6 do?

A

Phosphorylates and inactivates the cell inhibitory function of the retinoblastoma protein in cooperation with cyclin E/CDK2

28
Q

What does the retinoblastoma protein work with?

A

Cyclin E/CDK2

29
Q

What happens when the retinoblastoma protein is inhibited/phosphorylated?

A

Normally it stops the cell from replicating but when phosphorylated replication can be started

30
Q

What can cyclin D1 do?

A

Helps loosen the chromatin out and helps get replication started

31
Q

What is a retinoblastoma?
(2)

A

The retinoblastoma protein is a tumor suppressor protein that is dysfunctional in several major cancers.

One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide.

32
Q

Write a note on cyclin E
(4)

A

Binds to CDK2 in the G1 phase

Required for the transition from G1 to S phase

Cyclin E/CDK2 complex phosphorylates p27Kip1 (an inhibitor of cyclin D)

Phosphorylation of p27Kip1 tags it for degradation, promoting expression of cyclin A, allowing progression to S phase

33
Q

What does cyclin E bind to and when?

A

Binds to CDK2 in the G1 phase

Required for the transition from G1 to S phase

34
Q

What does Cyclin E/CDK2 complex?

A

Phosphorylates p27Kip1

35
Q

What is p26Kip1?

A

An inhibitor of cyclin D

36
Q

What happens when p26Kip1 is phosphorylated?
(2)

A

It is tagged for degradation

This promotes the expression of cyclin A which allows progression to S phase

37
Q

Write a note on cyclin A

A

It can activate two different CDKs, CDK2 or CDK1

It functions in both S-phase and mitosis

Helps trigger the G2/M transition

Levels increase with the onset of the S phase and contribute to the stimulation of DNA synthesis

In early mitosis it drives the initiation of chromosome condensation

37
Q

Write a note on cyclin A
(6)

A

It can activate two different CDKs, CDK2 or CDK1

It functions in both S-phase and mitosis

Helps trigger the G2/M transition

Levels increase with the onset of the S phase and contribute to the stimulation of DNA synthesis

In early mitosis it drives the initiation of chromosome condensation and nuclear envelope breakdown

CDK-cylin A activity peaks at G2/M

Inactivation of cyclin A arrests the cell cycle in G2

38
Q

When does Cyclin A function

A

It functions in both S-phase and mitosis

39
Q

What CDKs does cyclin A work with?

A

CDK2 or CDK1

40
Q

What does cyclin A trigger?

A

G2/M transition

41
Q

What does the cyclin A peak do?

A

Contribute to the stimulation of DNA synthesis

42
Q

What does cyclin A do in mitosis?

A

In early mitosis it drives the initiation of chromosome condensation and nuclear envelope breakdown

43
Q

What does cyclin A inactivation do?

A

Inactivation of cyclin A arrests the cell cycle in G2

44
Q

Write a note on cyclin B
(4)

A

A mitotic cyclin

Binds to CDK1

Activity of cyclin B/CDK1 complex rises through the cell cycle until mitosis then it falls abruptly due to degradation

The complex is called promoting factor or mitosis promoting factor (MPF)

45
Q

What phase does cyclin B work in?

A

Mitosis

46
Q

Describe the activity of cyclin B

A

Activity of cyclin B/CDK1 complex rises through the cell cycle until mitosis then it falls abruptly due to degradation

47
Q

What does cyclin B bind to?

A

CDK1

48
Q

What is cyclin B/CDK 1 complex also called?

A

Maturation Promoting Factor

Mitosis Promoting Factor

49
Q

Write a note on Mitosis Promoting Factor
(2)

A

In the 1970s cells in M phase contained an unknown factor that could force frog egg cells stuck in G2 phase to enter M phase

MPF was identified in 1980s to be a CDK bound to its M cyclin partner

50
Q

What is the APC complex?

A

The anaphase-promoting complex/cyclosome

51
Q

What does Mitosis promoting factor trigger?

A

The anaphase-promoting complex (APC)

52
Q

Write a note on the APC
(3)

A

A protein complex that causes M cyclins to be destroyed starting in anaphase

When M cyclins are destroyed it pushes the cell out of mitosis, allowing the new daughter cell to enter G1

The complex also causes the destruction of the proteins that hold the sister chromatids together, allowing them to separate in anaphase

2.1 Cell and Molecular Biology (26 decks)

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