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Biochemistry (Cole) > Lecture 37 Cell Cycle Control and Cell Division > Flashcards

Lecture 37 Cell Cycle Control and Cell Division Flashcards

1
Q

What does the cell cycle involve?

A
  • DNA replication and dividing the cell to create two identical daughter cells
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2
Q

What triggers the major events of the cell cycle?

A
  • the cell cycle control system
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3
Q

What controls cell proliferation?

A
  • cell cycle control machinery
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4
Q

What is cancer essentially?

A
  • uncontrolled proliferation
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5
Q

What are the three checkpoints in the cell cycle?

A
  • start checkpoint
  • G2/M checkpoint
  • Metaphase to anaphase transition
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6
Q

What does the start check point ask?

A
  • is the environment favorable
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7
Q

What does the G2/M checkpoint?

A
  • is all the DNA replicated

- Is environment favorable?

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8
Q

What does the metaphase to anaphase transition checkpoint ask?

A
  • are all the chromosomes attached to the spindle
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9
Q

what happens at the start checkpoint if its cleared?

A
  • enter cell cycle and proceed to S phase
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10
Q

What happens after G2/M phase?

A
  • enter mitosis
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11
Q

what happens after the metaphase to anaphase transition?

A
  • trigger anaphase and proceed to cytokinesis
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12
Q

What does the checkpoint system depend on?

A
  • cyclin dependent protein kinases (Cdks)
  • proteolytic events (protein degredation)
  • Transcriptional regualtion (kinases)
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13
Q

Essentially what is the cell cycle control system doing?

A
  • arrests the cycle whenever the cell fails to complete essential cell-cycle process or encounters unfavorable intracellular or extracellular conditions
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14
Q

G0 phase

A
  • resting phase
  • cells can permanently enter this resting phase (osteocytes)
  • terminally differentiated cells
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15
Q

What requires the the binding of cyclin and subsequent specific phosphorylation to become an active enzyme?

A
  • cyclin dependent kinase (Cdk)
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16
Q

In the absence of cyclin, cdk is _____?

A
  • inactive
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17
Q

What cyclin moves the cycle into S phase?

A
  • G1/S
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18
Q

What cyclin moves it through the S phase all the way to M phase?

A
  • s-cyclin
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19
Q

What cyclin moves the cycle through anaphase?

A
  • M- cyclin
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20
Q

Do the concentrations of Cdk change throughout the cell cycle?

A
  • no

- constitutive expression

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21
Q

What is critical for determining the transitions from one phase of the cell cycle to the next?

A
  • the appearance and disappearance of the various cyclins
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22
Q

What initiates the metaphase to anaphase transition?

A
  • anaphase promoting complex or cyclosome or (APC/C)
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23
Q

What moves the t loop away from the active site on cdk?

A
  • cyclin binding
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24
Q

When the t-loop binds the cdk is now _____ active?

A
  • partially active
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25
Q

What enzyme acts to fully activate cdk?

A
  • cdk-activating kinase
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26
Q

When is cdk fully active?

A
  • when the t-loop is phosphorylated
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27
Q

What is the prerequisite for downstream events of the cell cycle?

A
  • activation of the cyclin-cdk complex
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28
Q

Once cyclin-cdk is activated does the cell cycle proceed no matter what (uninterrupted)?

A
  • no there are other regulatory factors downstream
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29
Q

What could a mutation of the regulatory factor lead to?

A
  • potentially cancer

- just like mutations to cyclin or cdk function could lead to misregulation of the cell cycle

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30
Q

What happens when Wee1 kinase adds a second phosphate to active cdk?

A
  • it inactivates cdk
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31
Q

What enzyme is used to removed a 2nd phosphate and activate cdk?

A
  • Cdc25 phosphatase
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32
Q

the apc/c is a member of the ____ ligase family of proteins

A
  • ubiquitin
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33
Q

What is the function of APC/C?

A

catalyzes the ubiquitylation and degradation of securin and the S and M cyclins

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34
Q

What does securin do?

A
  • securin is involved in the protein linkages that hold the sister chromatids together
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35
Q

What does securin degredation lead to?

A
  • securin degradation leads to activation of a protease that then separates the sisters and unleashes anaphase
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36
Q

What does degredation of the S and M cyclins lead to?

A
  • inactivation of the cdks
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37
Q

What does loss of cdks mean?

A
  • that their targets can be dephosphorrylated by various phosphatases that are present in anaphase which completesM phase
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38
Q

When is APC/C activated?

A
  • mid-mitosis
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39
Q

When is APC/C turned off?

A
  • when G1/S-Cdks are activated in late G1?

- this allows for cyclin accumulation to start the next cell cycle

40
Q

What activates APC/C?

A
  • cdc20
41
Q

How does APC/C inactivate m-cyclin?

A
  • it attaches a polyubiquitin chain that is targeted for protein degradation
42
Q

What does SCF do?

A
  • it ubiquitylates cdk inhibitor (CKI) proteins in late G1 such as p27
  • (leads to activation of cell cycle)
43
Q

What is p27?

A

-it is a CKI family member that binds to active cyclin-cdk complex

44
Q

How does p27 make cdk complex innefecgtive?

A
  • it distorts the active site of Cdk and also inserts into the ATP binding site, further inhibiting the enzyme activity
45
Q

What is E1 and E2 role in degradation of CKI?

A
  • they assist in the additoon of multiple ubiquitin molecules to the CKI and this targets the protein for degradation in the proteosome complex
46
Q

What part of SCF complex binds to CKI?

A
  • f box protein is required for binding to specific protein targets
47
Q

What is the central component of the control system?

A
  • the series of cyclin-cdk complexes that regulate transitions through the various phases
48
Q

What is the inhibitory mechanisms role in cell cycle control?

A
  • provide information about the extracellular environment, DNA or cell damage, and whether each step in the cell-cycle has been properly completed.
49
Q

Is cyclin gene expression induced?

A

yes it is induced as the cell cycle transitions from one phase to the next

50
Q

Three key steps of cycle

A
  1. Induction of cyclins
  2. Proteolysis
  3. Transcriptional regulation
51
Q

What would DNA damage during the cell cycle lead to?

A
  • inhibitory mechanisms shutting the cycle down
52
Q

Why does G0 typically occur?

A
  • due to a lack of growth factors that a cell needs for the cell cycle
53
Q

When does G0 occur?

A
  • when cells reach maturity (some cells stay forever in this stage)
54
Q

What does the dREAM complex do?

A
  • binds exclusively to deacteylated histone
55
Q

What does E2F promote?

A
  • transcription
56
Q

Co-repressors of either E2F and pRB lead to:

A
  • histone modifications that result in histone compaction and suppression of gene expression
57
Q

what is the cell cycle control system designed to do?

A
  • block progression through each of the checkpoints if problems are sensed
58
Q

Does DNA replication occur at random or specific sites?

A
  • at specific sites or origins of replication
59
Q

What two steps is the initiation phase of DNA replication divided into?

A
  • Late mitosis-early G1: pre replication complex at the origins of replication
  • Onset of S phase when pre replication complex nucleates the formation of the pre initiation complex
60
Q

What are the parts of the prereplicative complex?

A
  • ORC
  • Cdc6 + Cdt1
  • Mcm (helicase)
61
Q

What is the initial step of S phase?

A
  • degredation of phosphorylated Cdc6

- inhibition of Cdt1 by geminin

62
Q

what triggers the initial step of S phase?

A
  • S- Cdk accumilation
63
Q

What is the second step of the s phase?

A
  • phosphorylation of ORC

- and binding of pre initiation complex (DNA polymerase)

64
Q

What is one of apcc role on late g2/m in regards to cdt1?

A
  • degrades geminin so that we can form the prereplicative complex again and keep replicating
65
Q

What leads to the formation of the pre initiation complex and initiation?

A
  • s-Cdk activation
66
Q

What does M-cdk activation lead to?

A
  • chromosome segregation
67
Q

What checkpoint insures that all of the DNA has been properly replicated?

A
  • G2-M checkpoint
68
Q

What drives entry into mitosis?

A
  • abrupt increases in M-Cdk activity at the G2-M checkpoint
69
Q

What does M-cdk induce?

A
  • assembly of mitotic spindle
  • chromosome condensation
  • promotes break down of the nuclear envelop
  • rearrangements of the actin cytoskeleton and the golgi apparatus
70
Q

Mitosis (1 hour) comprises five phases

A
  • prophase
  • prometaphase
  • metaphase
  • anaphase
  • telophase
71
Q

What happens in prohpase?

A
  • condensing replicated chromosome
  • mitotic spindle forms
  • centrosomes moving towards pole
72
Q

What attaches to the mitotic spindle?

A
  • kinetochore
73
Q

What happens in prometaphse?

A
  • breakdown of nuclear envelope

- chromosomes attach and start to align

74
Q

What happens in metaphase?

A
  • chromosomes align at equator

- everything lines up

75
Q

What happens anaphase?

A
  • the sister chromatids synchronously began to separate to form two daughter chromosomes.
  • ## microtubules are getting shorter
76
Q

What happens at telophase?

A
  • daughter chromosomes arrive at poles
  • begin to decondense
  • nuclear envelope reassembles
  • contractile rings form
77
Q

What happens in cytokinesis?

A
  • separation of two daughter cells
78
Q

What is ESCO2 role in the cell cycle?

A
  • it encodes an acetyltransferase that is important for the formation of the cohesion complex that binds to chromosomes and creates cohesion between sister chromatids
79
Q

What happens with ESCO2 mutations?

A
  • lead to decreased DNA transcription and subsequent ribosomal biogenesis and the observed defects in nuclear morphology
  • leads to decreased protein synthesis
  • roberts syndrome
80
Q

what type of feedback does active M-cdk have on Cdc25 and Wee1?

A
  • positive on both leading to more active M-cdk ?
81
Q

What happens when securin is degraded?

A
  • seperase is freed and activated and seperates chromatids by degraded adhesion proteins
82
Q

what stimulates cell division?

A

mitogens

83
Q

Mitogens

A
  • stimulate cell division mainly by stimulating G1/S-Cdk activity that inhibit intracellular negative controls that block progression through the cell cycle
84
Q

What do growth factors do?

A
  • stimulate cell growth(increase in cell mass) by stimulating protein synthesis and inhibiting protein degradation
85
Q

What do survival factors do?

A
  • suppress programmed cell death (apoptosis)
86
Q

How do mitogens trigger multiple intracellular signaling pathways?

A
  1. mitogen binds to mitogen membrance ceptor
  2. receptor activates ras
  3. ras activates MAP kinase
  4. activationn of gene regulatory protein
  5. immediate early gene expression
87
Q

what does immediate early gene expression lead to?

A
  • gene regulatory proeteins like Myc
88
Q

What does myc do?

A
  • myc is thought to promote cell cycle entry by increasing the expression of the genes encoding the G1 cyclins which results in increased G1-Cdk activity
89
Q

What does G1-cdk do in regards to regulation of cell cycle?

A
  • activates regulatory factors like E2F
90
Q

What inhibits E2F?

A
  • retinoblastoma protein
91
Q

How does G1-Cdk activate E2F?

A
  • it phosphorylates Rb rendering it inactive and reducing its binding to E2F
92
Q

What does E2F do?

A
  • drive S phase gene transcription
  • positive feed back on itself by phosphorylating rb
  • also synthesizes and activates S-Cdk
93
Q

What do growth factors do?

A
  • stimulate protein synthesis and or protein degradation
94
Q

What is epidermal growth factor signaling related to?

A
  • PI3 kinase/Akt signaling
95
Q

What protein does TGFB use?

A
  • smad protein
96
Q

What is smad protein target?

A
  • p21
  • p15
    (smad inhibits cyclins)
97
Q

TOR

A
  • gene regulatory factors
  • ribosome synthesis
  • protein synthesis and cell growth

Biochemistry (Cole) (25 decks)

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