Cell Cycle Control and Cell Division Flashcards
1
Q
The entry into mitosis in the cell cycle is triggered by what?
A
M-CDK mediated phosphorylation of specific proteins, along with protein kinases (2 families)
2
Q
How does G1-CDK activate the E2F proteins?
A
G1-CDK phosphorylates the Rb protein, releasing it from E2F
3
Q
Which component of the cell-cycle control system detects whether or not the chromosomes are attached to their spindles?
A
APC/C
4
Q
At what phase of the cell cycle are CDK4-cyclin D and CDK6-cyclin D active?
A
G1 phase
5
Q
The SMAD proteins target ___ and ___ to prevent cell cycle progression by inhibiting the cyclins.
A
p21; p15
6
Q
What does the cell cycle involve?
A
DNA replication and cell division to create two identical daughter cells
7
Q
How is the cell cycle controlled by proteolysis?
A
- inactive APC/C binds to CDC20 that activates it
- active APC/C initiates the binding of many ubiquitin molecules to the cyclin-CDK complex
- ubiquitin tags the cyclin-CDK for proteolysis
8
Q
___ signaling involves gene regulatory factors and ribosome synthesis to promote protein synthesis and cell growth.
A
m-TOR
9
Q
The MAPK leads to the activation of what?
A
activation of immediate early gene expression (genes turned on immediately after a mitogen binds to the receptor)
10
Q
Where is the second checkpoint?
A
at the end of G2, right before the M phase
11
Q
Is there an intact nuclear envelope still present during prophase?
A
YES
12
Q
TGF-B works through the ____ proteins.
A
SMAD
13
Q
____ interact with cell surface receptors on the cell surface, which leads to the activation of a kinase.
A
Mitogens
14
Q
At what phase is CDK2-cyclin A active?
A
middle of S phase
15
Q
The ___ cyclin is the protein that binds to S-CDK and moves the cell through the S phase.
A
S
16
Q
What part of the cyclin-CDK complex gets ubiquinylated?
A
cyclin
17
Q
The activity of cyclin-CDK is further regulated by Wee1 kinase. What does Wee1 kinase do?
A
Wee1 further phosphorylates cyclin-CDK to render it inactive
18
Q
What is the pathway of a mitogen-activated protein kinase (MAPK) signaling cascade?
A
stimulus»_space; MAPKKK»_space; MAPKK»_space; MAPK»_space; biological reponse
19
Q
How does the division of the cytoplasm occur?
A
by contractile rings
20
Q
What does the loss of CDKs mean after their inactivation?
A
M phase is completed (their targets can be dephosphorylated by various phosphatases present in anaphase)
21
Q
What CKI helps cells withdraw from the cell cycle when they terminally differentiate?
A
p27
22
Q
Why does p27 insert itself into the ATP-binding site of the cyclin-CDK complex?
A
to inhibit enzyme activity by preventing it from phosphorylating any targets
23
Q
What complex initiates the metaphase-anaphase transition?
A
Anaphase-Promoting Complex (APC/C)
24
Q
What kinase is primarily involved in suppressing CDK1 activity before mitosis by phosphorylating inhibitory sites?
A
Wee1 kinase
25
The metaphase-to-anaphase transition involves ___.
proteolysis
26
Binding of the CDK to its cyclin leads to what?
the movement of the T-loop away from the active site, leading to partial activation
27
What does M-CDK do to Wee1 kinase in its postive feedback mechanism?
inhibits Wee1 kinase; blocks this inhibitory kinase so more of the active form of M-CDK can be made
28
How many D cyclins are present in mammals?
3 (D1, D2, D3)
29
Each ___ can induce different effects at different times in the cell cycle, based upon the relative presence, absence, or abundance of each specific target.
cyclin-CDK
30
CDK requires the binding of ___ and ___ to become an active enzyme.
cyclin; subsequent specific phosphorylation
31
What are the partners of the G1-CDK complex?
cyclin D and CDK4, CDK6
32
What does the degradation of securin lead to?
the activation of a protease that separates the sister chromatids and unleashes anaphase
33
What tags the cyclin-CDK complex for degradation?
binding of many ubiquitin molecules to the cyclin by ubiquitylation enzymes
34
What are the two critical proteins that initiate the formation of the pre-replicative complex?
CDC6 and CDT1
35
What is CDT1 inhibited by?
geminin
36
What is cancer?
inappropriate proliferation
37
___ can phosphorylate the T-loop at a threonine residue in the T-loop and fully activate the cyclin-CDK complex.
CDK-activating kinase (CAK)
38
The accumulation of the S-CDK concentration initiates the degradation of ____.
phosphorylated CDC6
39
___ activates APC/C and maintains its activity through G1. It is inhibited by CDK activity.
CDH1
40
The activation of ___ triggers the events of mitosis, which includes chromosome segregation.
M-CDK
41
____ starts abruptly with the breakdown of the nuclear envelope. Chromosomes can now attach to spindle microtubules by their kinetochores.
Prometaphase
42
At what phase is CDK2-cyclin E active?
end of G1 phase
43
When does mitosis begin?
after the G2/M checkpoint has insured that all of the DNA has been replicated correctly
44
The ___ cyclin is the protein that moves the cell cycle forward from G1 to S.
G1/S
45
The initiation phase of DNA replication is divided into 2 steps. What are they?
- Late mitosis-early G1
| - Onset of S phase
46
Once E2F proteins are released and activated, it drives the formation and synthesis of ____.
C-cyclins and S-CDK
47
E2F and pRB proteins lead to the compaction of histones to form _____ in the dREAM complex, which renders the cell's DNA inactive.
heterochromatin (because the DNA now cannot be transcribed)
48
Which complex assesses whether or not the cellular environment is favorable?
G1-CDK
49
In what phase is the pre-replicative complex disassembled?
S phase
50
The ____ stimulate cell division mainly by stimulating G1/S-CDK activity that inhibits intracellular negative controls.
mitogens
51
What are the critical determinants of cancer progression in the cell cycle?
genes involved in cell-cycle regulation and control
52
What is the S phase?
where DNA is replicated
53
When abrupt increase of activity drives entry into mitosis?
M-CDK
54
What is the origin of replication bound by in the phases of the cell cycle where it is inactive?
various proteins to block the site
55
The dREAM complex puts itself into which phase of the cell cycle?
G0
56
What are the partners of the G1/S-CDK complex?
cyclin E and CDK2
57
What is the M phase?
where cells divide
58
___ induces the assembly of the mitotic spindle, chromosome condensation, breakdown of the nuclear envelope, and rearranges the actin cytoskeleton and Golgi.
M-CDK
59
What are the two sister chromatids held together by?
kinetochores
60
What allows for cyclin accumulation to start the next cell cycle?
when the G1/S-CDKs are activated in late G1, APC/C is turned off
61
At each checkpoint, the main cyclin increases in concentration and then decreases as the next phase's cyclin ___ in concentration.
increases
62
Where is APC/C activated at?
in mid-mitosis
63
___ 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.
Myc
64
After the degradation and inhibition of CDC6 and CDT1, the pre-initiation complex arrives and phosphorylates the ____ on the DNA strand so DNA replication can occur.
origin proteins
65
Activation of cyclin-CDK is a prerequisite for many downstream events. A mutation in any of these downstream, tight regulations can lead to ___.
cancer
66
How many major cell cycle checkpoints do eukaryotic cells have?
3
67
Where is the metaphase-to-anaphase transition?
within the M phase
68
What are the extracellular signals controlling cell division?
mitogens
growth factors
survival factors
69
What is the importance of checkpoints in the cell cycle?
to make sure the phase in complete before moving on to the next phase
70
What system can arrest the cell cycle whenever a cell fails to complete a process or encounters unfavorable intracellular or extracellular conditions?
the cell-cycle control system
71
What kinase is required for the FULL activation of the cyclin-CDK complex?
CDK-activating kinase (CAK)
72
What happens during the onset of the S phase of DNA replication?
the pre-replication complex nucleates the formation of the pre-initiation complex
73
At what phase of the cell cycle is CDK1-cyclin B active?
M phase
74
____ stimulate cell growth by stimulating protein synthesis and inhibiting protein degradation.
Growth factors
75
What constituents does a fully active cyclin-CDK contain?
CDK
cyclin
activating phosphate
76
What does the F-box domain of the SCF complex do to CKI molecules?
initiate the ubiquitylation of CKI to tag it for proteolysis
77
In what phase is APC/C active and CDK is inactive?
G1
78
In ____, the replicated chromosomes consisting of two sister chromatids condense. The mitotic spindle begins to assemble between the two centrosomes.
prophase
79
What are the three types of control the cell-cycle checkpoint system depends on?
- use of protein kinases (CDKs) for phosphorylation
- proteolytic events
- transcriptional regulation
80
What triggers the major events of the cell cycle?
the cell-cycle control system
81
___ tend to work through the PIP3 signaling mechanisms.
Growth factors
82
Why is EACH cyclin partner important in the cell cycle?
because each one determines a different and specific target and then determines which one is subsequently phosphorylated by the CDK subunit
83
In a CDK's inactive state, the active or catalytic site is blocked by what?
the presence of a region called the T-loop
84
During cytokinesis, the re-formation of the ____ array of microtubules nucleated by the centrosome occurs.
interphase
85
What general mechanisms determine the movement of cells through the cell cycle?
- concentration
- phosphorylation state
- binding partners
86
Do the concentrations of the CDK change?
NO - constitutive expression
87
___ has the ability to block rereplication of DNA if it is damaged.
M-CDK
88
What are the partners of the M-CDK complex?
cyclin B and CDK1
89
Which complex detects DNA damage and halts the cell cycle?
G1/S-CDK, S-CDK and M-CDK
90
The cyclin-CDK complexes are also regulated by ___ mechanisms, such as information about DNA damage, step completion, or extracellular environment.
inhibitory
91
In ____, the sister chromatids separate to form two daughter chromosomes. Chromosome segregation begins in this phase as microtubules get shorter.
Anaphase
92
What triggers the ubiquitylation reaction on the cyclin-CDK to tag it for proteolysis?
activation of APC/C by CDC20
93
____ catalyzes the ubiquitylation and degradation of securin and the S- and M-cyclins.
APC/C
94
In the absence of cyclin, CDK is ____.
in an inactive state
95
What is the G1 phase?
resting phase
96
What does the metaphase-to-anaphase checkpoint do?
make sure all chromosomes are attached to spindles to trigger anaphase and proceed to cytokinesis
97
What does M-CDK do to CDC25 in its positive feedback mechanism?
it stimulates more CDC25 to go from the inactive state to the active state to produce more active M-CDK
98
What is the G2 phase?
the phase between the S phase and M phase
99
What only partly activates the cyclin-CDK complex?
the movement of the T-loop away from the active site
100
___ suppress programmed cell death and prevent apoptosis.
Survival factors
101
How is cyclin gene expression regulated?
specific cyclin genes are induced or "turned on" by transcriptional activity
102
What are the partners of the S-CDK complex?
cyclin A and CDK2, CDK1
103
What is critical for determining the transitions from one phase to another in the cell cycle?
the appearance and disappearance of the various cyclins
104
Where is the first ("start") checkpoint?
at the end of the G1 phase, right before the S phase
105
In ____, the chromosomes align at the equator of the spindle. The kinetochores attach sister chromatids to opposite poles of the spindle.
metaphase
106
What molecules assist in the ubiquitylation of CKI (and cyclin)?
E1, E2 and ubiquitin
107
___ is inactivated by the binding to the active Rb protein.
E2F
108
What partner does a CDK rely on to become an active enzyme?
cyclin (= 2 subunit protein)
109
The activation of what enzyme allows the transition of metaphase to anaphase?
separase
110
One of the key functions of G1-CDK is to activate the ___ proteins that are themselves regulatory factors.
E2F
111
What protein does the cell-cycle checkpoint control system depend on?
cyclically activated cyclin-dependent protein kinases (CDKs)
112
What does SCF ubiquinylate?
CDK-inhibitor (CKI) proteins in late G1 (ex: p27)
113
p27 is an example of a ___ protein.
CDK-inhibitor (CKI)
114
What are the three checkpoints in the eukaryotic cell cycle?
Late G1/Start checkpoint
G2/M checkpoint
Metaphase-to-anaphase transition
115
Which phase of the cell cycle is a quiescent or resting phase?
G0
116
What does the contractile ring create?
a cleavage furrow
117
When the ___ concentration accumulates, it triggers S phase.
S-CDK
118
What are the two positive feedback loop mechanisms of M-CDK activity?
- active M-CDK stimulates the activation of CDC25
| - active M-CDK inhibits Wee1 kinase
119
What are the first genes that get turned on by the MAPK activation by mitogen binding called?
immediate early genes
120
What ubiquitin ligase catalyzes the ubiquitylation of CKI involved in G1 control, such as through the phosphorylation of it?
SCF
121
What system ensures the proper timing, order, and fidelity of cellular events?
the cell-cycle control system
122
What enzyme can reverse the affects of Wee1 kinase on cyclin-CDK?
CDC25 phosphatase
123
When are the inhibitory mechanisms of the cell-cycle control system initiated?
when there is damage detected or the environment is unfavorable
124
What complex is bound to CDC6 and CDT1 in the pre-replicative complex?
MCM (helicase)
125
___ catalyzes ubiquitylation of regulatory proteins involved at the end of mitosis, such as securin and S- and M-cyclins.
APC/C
126
The ___ on active SCF complex recognizes phosphorylated CDK-inhibitor proteins (CKI).
F-box
127
The degradation of what leads to inactivation of the CDKs?
S- and M-cyclins
128
The cell-cycle control machinery controls ____.
cell proliferation
129
Do growth factors directly or indirectly lead to cell growth and cell division?
BOTH - can be linear or direct in their mechanisms depending on the protein
130
What is the preferred signaling pathway of EGF?
PI3 kinase/Akt signaling
131
During the metaphase-anaphase transition, M-CDK drives the activation of ___.
APC/C
132
What specific sites does DNA replication occur at?
origins of replication
133
What does EGF eventually promote?
cell survival
| protein synthesis
134
___ triggers the initial activation of APC/C at the metaphase-anaphase transition.
CDC20
135
What type of complex that binds the two sister chromatids in affected in Roberts syndrome?
acetyltransferase important for the formation of the cohesion complex
136
The ___ triggers the events that occur in each phase of the cell cycle.
cell-cycle control system
137
Can cells enter G0 permanently?
YES
138
APC/C activity changes during the cell cycle due to its interactions with ___ and ___.
CDC20 (anaphase); CDH1 (late mitosis to G1)
139
What is a key step in the initiation of protein degradation by the proteasome complex?
ubiquitylation
140
What cohesion protein is involved in protecting protein linkages that hold the sister chromatids together?
securin
141
Myc is an ___.
immediate early gene
142
At what phase is CDK1-cyclin A active?
end of S phase
143
Which complex detects if there is unreplicated DNA?
M-CDK
144
The ___ cyclin begins to increase in concentration from the G2/M checkpoint to reach the metaphase-anaphase transition.
M
145
The ____ kinase phosphorylates an activating site in CDKs.
CDK-activating (CAK)
146
Does the cell-cycle control system respond to intracellular and extracellular signals?
YES
147
___ is stimulated by M-CDK activity.
CDC20
148
What does the G2/M checkpoint do?
make sure all the DNA has been replicated before proceeding to the M phase for mitosis
149
___ binds to both subunits of the active cyclin-CDK complex, distorting the active site of CDK and inserting itself into the ATP-binding site to inhibit enzyme activity.
p27
150
What is the central component of the cell-cycle control system?
the series of cyclin-CDK complexes that regulate the transitions through the various phases
151
The concentrations of the three major cyclin proteins oscillate during the cell cycle because their expression is induced to promote the ____ through the cell cycle.
transitions
152
What happens during the late mitosis-early G1 phase of DNA replication?
the pre-replication complex assembles at the origins of replication
153
Passage through the Start checkpoint of the cell cycle initiates ____ and the S phase of the cell cycle.
DNA replication
154
Roberts syndrome results from the decreased ____ and eventual decreased protein synthesis.
rDNA transcription
155
In the ___ phase, APC/C complex targets the geminin protein by degrading it and allows the accumulation of CDT1, forming a new pre-replication complex.
G2/M
156
Cyclin gene expression is controlled and regulated by ____.
transcription
157
At what phase of the cell cycle are heart cells, osteocytes, and neural cells perpetually terminally differentiated at?
G0
158
The activation of APC/C leads to the formation of a complex of ___ and ___, which then leads to the degradation of securin.
securing; inactive separase
159
What enzyme is primarily involved in controlling CDK1 activation at the onset of mitosis by removing inhibitory phosphates from CDKs?
CDC25 phosphatase
160
___ is an ubiquitin ligase similar to APC/C that contains 3 subunits.
SCF
161
Why does the entrance into G0 usually occur?
due to lack of growth factors or nutrients (or when terminally differentiated)
162
During ____, the two daughter chromosomes arrive at the poles of the spindle and decondense. A new nuclear envelope forms around each set. Division of cytoplasm begins with contraction of contractile ring.
telophase
163
Where do cells enter G0 at?
from a cell-cycle checkpoint in the G1 phase
