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D1 Fall - Biochem > 10/26: Cell-cycle Control and Cell Division I > Flashcards

10/26: Cell-cycle Control and Cell Division I Flashcards

1
Q

What does the cell cycle involve?

A

DNA replication + Cell division

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2
Q

What does the cell cycle create?

A

Two identical daughter cells

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3
Q

What does the cell-cycle control system trigger?

A

Major events of the cell cycle

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4
Q

What occurs to ensure that each phase is complete before the next one begins?

A

Series of transitions or checkpoints

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5
Q

How many major checkpoints in eukaryotic cells?

A

3

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6
Q

What does the cell-cycle control machinery control?

A

Cell proliferation

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7
Q

What is cancer essentially?

A

Inappropriate proliferation

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8
Q

Many of the genes (proteins) involved in cell-cycle regulation are critical determinants of?

A

Cancer progression

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9
Q

What are the phases of mitosis?

A
  1. Prophase
  2. Metaphase
  3. Anaphase
  4. Telophase
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10
Q

What is the starting checkpoint of the cell-cycle?

A

Enter cell cycle and proceed to S phase
Is environment favorable?

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11
Q

What is the second checkpoint of the cell-cycle?

A

G2/M Checkpoint
- from here enter mitosis
Is all DNA replicated?
Is environment favorable?

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12
Q

What is the third checkpoint of the cell-cycle?

A

Metaphase-to-anaphase transition
- trigger anaphase and proceed to cytokinesis
Are all chromosomes attached to the spindle?

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13
Q

What occurs at the G1 checkpoint?

A

Check for:
nutrients
growth factors DNA damage

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14
Q

What occurs at the G2 checkpoint?

A

Check for:
Cell size
DNA replication

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15
Q

What occurs at the metaphase checkpoint?

A

Check for:
Chromosome spindle attachment

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16
Q

What does the cell-cycle checkpoint control system depend on?

A
  1. Clinically activated cyclin-dependent protein kinases (Cdks)
  2. cyclical proteolytic events
  3. transcriptional regulation
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17
Q

What does the cell-cycle control system ensure?

A

Proper timing, order, and fidelity of the events

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18
Q

What does the cell-cycle control system respond to?

A

Intracellular and extracellular signals

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19
Q

When does the cell-cycle control system arrest?

A

Whenever the cell fails to complete an essential cell-cycle process or encounters unfavorable intracellular or extracellular conditions

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20
Q

What do Cdk’s require to become an active enzyme?

A

Binding of cyclin and specific phosphorylation

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21
Q

In the absence of cyclin, what state is Cdk in?

A

Inactive

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22
Q

When the four major cyclin proteins oscillate during cell cycle, their expression is induced to promote:

A

Transitions through the cell cycle

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23
Q

Does the concentration of Cdk change?

A

No (constitutive expression)

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24
Q

What are the appearance and disappearance of the various cyclins critical for?

A

Determining the transitions from one phase of the cell-cycle to the next

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25
Q

What does the anaphase-promoting complex cyclosome (APC/C) initiate?

A

Metaphase to anaphase transition

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26
Q

What are the 3 D cyclins in mammals?

A

D1
D2
D3

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27
Q

In the inactive state the catalytic or active site of the cyclin-dependent kinase is blocked by the presence of?

A

A region called the T-loop

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28
Q

What does binding of the specific cyclin to its cognate cyclin-dependent kinase lead to?

A

Movement of the T-loop away froma ctive site, leading to partial activation

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29
Q

What does Cdk-activating kinase (CAK) phosphorylate?

A

T-loop at a threonine residue in the T-loop resulting in full activation of the cyclin-Cdk

30
Q

What is important for determining which specific targets are subsequently phosphorylated by the Cdk subunit?

A

Each cyclin partner

31
Q

What can each cyclin-Cdk induce?

A

Different effects at different times in the cell-cycle

32
Q

What is a prerequisite for downstream events?

A

Activation of the Cyclin-Cdk complex

33
Q

What is the activity of cyclin-Cdk regulated by?

A

Wee1 kinase

34
Q

What does Wee1 kinase further phosphorylate?

A

Cdk and renders it inactive

35
Q

What dephosphorylates and restores activity?

A

Cdc25 phosphate

36
Q

What is anaphase-promoting complex or cyclosome (APC/C) a member of?

A

Ubiquitin ligase family of proteins

37
Q

What does APC/C catalyze?

A

The ubiquitylation and degredation of securin and the S- and M-cylins

38
Q

What does securin do?

A

Protect the protein linkages that hold the sister chroatids together

39
Q

What does securin degredation lead to?

A

Activation of a protease that separates the sisters and unleashes anaphase

40
Q

What does degradation of the S- and M- cyclins lead to?

A

Inactivation of the Cdks

41
Q

What does loss of Cdks mean?

A

Their targets can be dephosphorylated by various phosphates that are present in anaphase, which completes M phase

42
Q

When is APC/C activated and remain active?

A

Mid-mitosis; remains active in G1

43
Q

What occurs when G1/S-Cdks are activated in late G1?

A

APC/C is turned off

44
Q

When APC/C is turned off what does this allow for?

A

Cyclin accumulation to start the nexy cell-cyvle

45
Q

When does APC/C activity change?

A

During cell cycle due to its interactions with Cdc20 in anaphase and Cdh1 fro late mitosis through early G1

46
Q

What family is SCF (Skp1, Cullins, F-box proteins)?

A

Ubiquitin ligase

47
Q

What 3 subunits does SCF contain?

A

S, C and F

48
Q

What is the function of SCF?

A

Ubiquitylates Cdk inhibitor (CKI) proteins in late G1 such as p27

49
Q

What is the key step in the initiation of many proteins “marked” for degradation by the proteasome complex?

A

Ubiquitylation

50
Q

What does p27 bind to?

A

Active cyclin-Cdk complex
The cyclin and Cdk subunits

51
Q

What does binding of p27 do?

A

Distorts the active site of Cdk

52
Q

Where does p27 insert into and leads to?

A

ATP-binding site; inhibits enzyme activity

53
Q

What does SCF associate with and what is this required for?

A

F-box protein; binding to specific protein targets

54
Q

What proteins assist in the addition of multiple ubiquitin molecules to the CKI?

A

proteins E1 and E2

55
Q

What targets the protein for degradation in the proteosome complex?

A

E1 and E2 addition to CKI

56
Q

When is cyclin gene expression regulated and specific cyclins induced?

A

As the cell cycle transitions from one phase to the next

57
Q

What is the central component of the control system?

A

Series of cyclin-Cdk complexes that regulate transitions through the various phases

58
Q

What are the complexes also regulated by?

A

Various inhibitory mechanisms

59
Q

What do inhibitory mechanisms provide information about?

A

Extracellular environment, DNA or cell damage and whether each step in the cell-cycle has been properly completed

60
Q

What does G0 represent

A

Resting or quiescent state

61
Q

How long can cells remain in G0?

A

Days to weeks or longer

62
Q

Can cells enter G0 permanently?

A

Yes until it dies

63
Q

When do cells enter G0 phase?

A

From a cell-cycle checkpoint in G1 phase

64
Q

Why does G0 phase occur?

A

Due to a lack of growth factors or nutrients

65
Q

In what cells does G0 maturitiy occur?

A

When they reach maturity
i.e., become terminally differentiated: nerve cells, heart muscle cells, and osteocytes

66
Q

What does the dREAM complex bind?

A

Exclusively to deacetylated histone H4

67
Q

What do E2F associated co-factors promote?

A

Transcription

68
Q

What do co-repressors of E2F and pRB lead to?

A

Histone modifications that result in histone compaction and suppression of gene expression

69
Q

What is a family of protein kinases involved in control of cell-cyvle?

A

Cdks

70
Q

What is a family of proteins that regulate Cdk activity?

A

Cyclin

71
Q

What is a complex of proteins involved in cel cycle control arrest and senscence by binding to the E2F family of transcription factors?

A

dREAM

72
Q

Hi

A

D1 Fall - Biochem (29 decks)

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