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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
What does the anaphase-promoting complex cyclosome (APC/C) initiate?
Metaphase to anaphase transition
26
What are the 3 D cyclins in mammals?
D1 D2 D3
27
In the inactive state the catalytic or active site of the cyclin-dependent kinase is blocked by the presence of?
A region called the T-loop
28
What does binding of the specific cyclin to its cognate cyclin-dependent kinase lead to?
Movement of the T-loop away froma ctive site, leading to partial activation
29
What does Cdk-activating kinase (CAK) phosphorylate?
T-loop at a threonine residue in the T-loop resulting in full activation of the cyclin-Cdk
30
What is important for determining which specific targets are subsequently phosphorylated by the Cdk subunit?
Each cyclin partner
31
What can each cyclin-Cdk induce?
Different effects at different times in the cell-cycle
32
What is a prerequisite for downstream events?
Activation of the Cyclin-Cdk complex
33
What is the activity of cyclin-Cdk regulated by?
Wee1 kinase
34
What does Wee1 kinase further phosphorylate?
Cdk and renders it inactive
35
What dephosphorylates and restores activity?
Cdc25 phosphate
36
What is anaphase-promoting complex or cyclosome (APC/C) a member of?
Ubiquitin ligase family of proteins
37
What does APC/C catalyze?
The ubiquitylation and degredation of securin and the S- and M-cylins
38
What does securin do?
Protect the protein linkages that hold the sister chroatids together
39
What does securin degredation lead to?
Activation of a protease that separates the sisters and unleashes anaphase
40
What does degradation of the S- and M- cyclins lead to?
Inactivation of the Cdks
41
What does loss of Cdks mean?
Their targets can be dephosphorylated by various phosphates that are present in anaphase, which completes M phase
42
When is APC/C activated and remain active?
Mid-mitosis; remains active in G1
43
What occurs when G1/S-Cdks are activated in late G1?
APC/C is turned off
44
When APC/C is turned off what does this allow for?
Cyclin accumulation to start the nexy cell-cyvle
45
When does APC/C activity change?
During cell cycle due to its interactions with Cdc20 in anaphase and Cdh1 fro late mitosis through early G1
46
What family is SCF (Skp1, Cullins, F-box proteins)?
Ubiquitin ligase
47
What 3 subunits does SCF contain?
S, C and F
48
What is the function of SCF?
Ubiquitylates Cdk inhibitor (CKI) proteins in late G1 such as p27
49
What is the key step in the initiation of many proteins "marked" for degradation by the proteasome complex?
Ubiquitylation
50
What does p27 bind to?
Active cyclin-Cdk complex The cyclin and Cdk subunits
51
What does binding of p27 do?
Distorts the active site of Cdk
52
Where does p27 insert into and leads to?
ATP-binding site; inhibits enzyme activity
53
What does SCF associate with and what is this required for?
F-box protein; binding to specific protein targets
54
What proteins assist in the addition of multiple ubiquitin molecules to the CKI?
proteins E1 and E2
55
What targets the protein for degradation in the proteosome complex?
E1 and E2 addition to CKI
56
When is cyclin gene expression regulated and specific cyclins induced?
As the cell cycle transitions from one phase to the next
57
What is the central component of the control system?
Series of cyclin-Cdk complexes that regulate transitions through the various phases
58
What are the complexes also regulated by?
Various inhibitory mechanisms
59
What do inhibitory mechanisms provide information about?
Extracellular environment, DNA or cell damage and whether each step in the cell-cycle has been properly completed
60
What does G0 represent
Resting or quiescent state
61
How long can cells remain in G0?
Days to weeks or longer
62
Can cells enter G0 permanently?
Yes until it dies
63
When do cells enter G0 phase?
From a cell-cycle checkpoint in G1 phase
64
Why does G0 phase occur?
Due to a lack of growth factors or nutrients
65
In what cells does G0 maturitiy occur?
When they reach maturity i.e., become terminally differentiated: nerve cells, heart muscle cells, and osteocytes
66
What does the dREAM complex bind?
Exclusively to deacetylated histone H4
67
What do E2F associated co-factors promote?
Transcription
68
What do co-repressors of E2F and pRB lead to?
Histone modifications that result in histone compaction and suppression of gene expression
69
What is a family of protein kinases involved in control of cell-cyvle?
Cdks
70
What is a family of proteins that regulate Cdk activity?
Cyclin
71
What is a complex of proteins involved in cel cycle control arrest and senscence by binding to the E2F family of transcription factors?
dREAM
72
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D1 Fall - Biochem (29 decks)

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