Cell Cycle Control And Cell Division Part I- Exam IV Flashcards
The cell cycle involves what two phases in order to create two identical daughter cells:
- Replication phase
- Division phase
What triggers the major events of the cell cycle?
Cell cycle control system
As the cell cycle proceed a serious of ___ ensure that each phase is complete before the next one begins
Checkpoints
How many major checkpoints are the eukaryotic cell cycle
3
What controls cell proliferation?
Cell-cycle control machinery
Inappropriate cell proliferation:
Cancer
Many of the genes (proteins) involved in the cell cycle regulation are critical:
Determinants of cancer progression
G1 and G2 are the ____ phases of the cell cycle
Gap phases
Phase of the cell cycle where DNA synthesis takes place:
S phase
Phase of the cell cycle in which division takes place
M phase
The 3 important checkpoints of the cell cycle occur during:
- Late G1checkpoint
- G2M checkpoint
- Metaphase to anaphase transition checkpoint
Checkpoint in late G1 checks for:
if the environment is favorable for cell division
In the late G1 checkpoint, what is being checked in the environment?
- Hormone signals
- Appropriate nutritions
- Etc
The G2M checkpoint:
Replication of DNA & favorable environment
If at the G2M checkpoint, the cell determines it can go on it will enter:
M phase
The cell won’t separate the chromosomes and split without the go ahead from the:
Metaphase to anaphase transition checkpoint
Check point that asks: Is the environment favorable?
Late G1 checkpoint (start checkpoint)
Check point that asks: Is all the DNA replicated? Is the environment favorable?
G2/M checkpoint
Check point that asks:
Are all the chromosomes attached to the spindle?
Metaphase to anaphase transition checkpoint
After the G1S checkpoint, the cell proceeds to:
After the G2M checkpoint, the cell proceeds to:
After the metaphase to anaphase transition checkpoint, the cell enters:
- Enters cell cycle and proceeds to S phase
- Enters mitosis
- Triggers anaphase and proceeds to cytokinesis
The cell-cycle checkpoint control system depends on:
- Cyclically activated cyclin-dependent protein kinases (CDKs)
- Cyclical proteolytic events
- Transcriptional regulation
Triggers the events that occur in each phase of the cell cycle:
Cell-cycle control system
The cell-cycle control system ensures the proper ____, ____, and ______ of the events.
Timing, order, fidelity
What type of signals does the cell-cycle control system respond to?
Intracellular & extracellular signals
Whenever the cell fails to complete an essential cell-cycle process or encounters unfavorable intracellular or extracellular conditions, the cell-cycle control system:
Arrests
Important critical determinants of the mammalian cell cycle:
Cyclin- CDKs
Where the cell gets pulled out of the normal cell cycle and is put into a quiescent state:
G0
Cyclins and cyclin dependent kinases are critical determinants for the transition of:
One cell cycle phase to the next
For cyclin dependent kinases to become activated, what event must first occur:
The binding of the specific cyclin that recognizes the CDK creating a complex
Following the binding of the specific cycling to the CDK creating a complex, what takes place?
Subsequent specific phosphorylation reactions
The specific phosphorylations that take place on the cyclin-CDK complex, turn this complex into an:
Activated state
If the cyclin is not present, the CDK will be:
Inactive
The initial checkpoint that occurs in late G1 involves what cyclin?
G1/S cyclin pair
The G1/S cyclin pair comes up and reaches a peak in ______, and when the cell moves from G1 into S this cyclin_____.
Late G1; falls off
The S-cyclin is necessary for:
Starting synthesis
As the G1/S cyclin is falling off, the S-cyclin:
Begins to work
As we reach into the mitosis phase, the S-cyclin ______, and an M cyclin has reached a ____,
Falls off; critical level
When does the M-cyclin level decrease?
Metaphase to anaphase transitions
The cyclin molecules ____ in their concentration because they are ____.
Oscillate ; Induced
_____ has the enzymatic activity in the cell cycle:
CDKs
The concentrations of the three major cyclin proteins oscillate during the cell cycle; their expression is _____ to promote transitions through the cell cycle
Induced
The concentrations of CDK do not change because they are:
Constitutively expressed
Critical for determining transitions from one phase of the cell-cycle to the next:
Appearance and disappearance of cyclins
In addition to the specific necessary cyclins, the _______ or ______ initiates the metaphase to anaphase transition.
Anaphase-promoting complex or Cylcosome (APC/C)
There are 3 D cyclins in mammals including:
Cyclins D1, D2, and D3
During the cell cycle process, the CDKs are consituitively expressed in an:
Inactive state
The CDKs only become activated if the:
Proper cyclin molecule is expressed
Why are the CDKs originally inactive?
Because the active site is blocked by T-loop
What molecule is the T-loop covering and on?
CDK
The T-loop folds over the active site and prevents it from:
Phosphorylating or doing its action
When the cyclin binds to the CDK, this causes the T-loop to:
Change its configuration
When the T-loop changes it configuration due to the binding of the cyclin, this results in:
A partially activated molecule
In order for the CDK to become fully activated, there is an enzyme called ______ that comes in and phosphorylates the T-loop
CDK activating kinase (CAK)
The CAK is responsible for:
Phosphorylating the T-loop
Where does the CAK phosphorylate the T-loop?
At a very specific threonine
When the threonine of the T-loop gets phosphorylated by the CAK this results in:
Fully activated CDK
List the basic steps of the activation of CDK:
- Cyclin binds
- T-loop moves
- CAK phosphorylates
- Fully active CDK
Each cyclin partner is important for determining which specific are subsequently:
Phosphorylated by the CDK subunit
Each cyclin-CDK can induce different effects at different times in the cell-cycle based upon the relative:
Presence, absence or abundance of each specific target
Activation of the cyclin CDK complex is a prerequisite for:
Downstream events
The activity of each cyclin-CDK complex is finely regulated by:
additional mechanisms
Just as mutations that alter cyclin or CDK function can lead to misregulation of the cell cycle, so to can mutations that disrupt any of these regulatory mechanisms creating the possibility that a:
Cancer of some type may occur
The fine tuning of the activation of the cyclin-CDK is controlled by the two enzymes:
Wee1 Kinase & Cdc25 Phosphatase
Phosphorylates a second site on the CDK molecule and renders it inactive
Wee1 Kinase
What enzymes is opposed by CDC25 phosphatase
Wee1 Kinase
Removes the inhibitory phosphate & puts the cyclin-CDK back into an active state:
Cdc25 Phosphatase
The Wee1kinase and the Cdc25phosphatase gives a ______ level of regulation
Rapid
Two important groups of proteins in the cell cycle with respect to proteolysis:
APC/C & SCF
APC/C is a member of the:
Ubiquities ligase family of proteins
Anytime ubiquitin molecules get added to a protein, this flags it for:
Degradation
APC/C is important in the degradation of:
Securin & the S- and M- cyclins
Securin is involved in protecting the ____ that hold the ____ together.
Protein linkages; sister chormatids
Securin degradation leads to the activation of a _____ that then separates the sisters and unleashes ____.
Protease ; anaphase
Degradation of the S- and M- cyclins leads to inactivation of the:
CDKs
Loss of the CDKs means that their targets can be _______ by various ______ present in anaphase.
De phosphorylated; phosphatases
The loss of the CDKs and the dephosphorylation of their targets by various phosphatases that are present in anaphase completes:
M phase
APC/C is activated in _____ and remains active in ____
Mid-mitosis ; G1
APC/C is activate din mid mitosis and remains active in G1 which provides a period in which:
CDK is inactive
When the G1/S-CDKs are activated in late G1, _____ is turned off.
APC/C
When the G1/S-CDKs are activated in late G1, APC/C is turned off allowing for:
Cyclin accumulation to start the next cell cycle
APC/C activity changes during the cell cycle due to its interactions with ____ in anaphase and ____ from late mitosis through early G1
CDC20 & Cdh1
Ubiquination leads to degradation by the:
Proteosome complex
SCF is a:
Ubiquitin ligase
SCF contains what subunits:
S, C, F subunits
SCF ubiquitylates:
CDK inhibitor proteins (CKI)
SCF ubiquitylates CDK inhibitor proteins in:
Late G1
A common CDK inhibitor protein:
p27
The ubiquination of the CDK inhibitor Preston’s allows the cell to transition from ____ to ____ as the G1/S cyclin comes up
G1 to S phase
P27 _____ the active cyclin-CDK complex
Inhibits
One portion of the P27 CDK inhibitor protein binds to ______ while the other portion binds to _____ of the cyclin-CDK complex
CDK portion; cyclin portion
Where the P27 binds to the CDK protein this occurs at the:
Active site of CDK
The p27 inactivation of the cyclin-CDK complex is a very:
Stable
The most important subunit of the active SCF complex:
F-box protein
The F-box proteins recognize the ______ when those proteins become phosphorylated
CDK inhibitory proteins (CKI)
When the F-box proteins recognizes the phosphorylated CKI, this causes the CKI to get:
Ubiquinated
The f-box recognizing the CKI resulting in ubiquination of the CKI ultimately resulting in its:
Degredation
You have fine level regulation of the cyclin CDK complex by:
You can also physically remove the inhibitory proteins present by:
Phosphorylation/dephosphorylation reactions
Ubiquitination process by APC/C or SCF
The cyclin genes are:
Inducible
When the cyclin genes get induced at the correct time, the cell-cycle:
Will move into next phase
Phosphorylates the activating site in CDKs:
CDK-activating kinase (CAK)
Phosphorylates inhibitory sites in CDKs; primarily involved in suppressing CDK1 activity before mitosis:
Wee1 kinase
Removes inhibitory phosphates from CDKs; three family members (A B and C) in mammals; primarily involved in controlling CDK1 activation at the onset of mitosis
Cdc25 phosphatase
Common CDK inhibitor proteins (CKIs)
Sic1, p27, p21, and p16
Catalyzes ubiquitylation of regulatory proteins involved primarily in exit from mitosis, including securin, S- and M- cyclins; regulated by association with activating subunits
APC/C
APC/C activating subunit in all cells; triggers initial activation of APC/C at metaphase-to-anaphase transition; stimulated by m-CDK activity
CDC20
APC/C activating subunits that maintains APC/C activity after anaphase and throughout G1; inhibited by CDK activity
Cdh1
Catalyzes ubiquitylation of regulatory proteins involved in G1 control, including some CKIs; phosphorylation of target protein usually required for acticity
SCF
A CDK inhibitor protein (CKI) that suppresses G1/S-CDK and S-CDK activities in G1; helps cells withdraw from cell cycle when they terminally differentiate, and phosphorylation by CDK2 triggers its ubiquitylation by SCF
P27
The central component of the control system is a series of ____ that regulate transitions through the various phases.
Cyclin-CDK complexes
The cyclin-CDK complexes are also regulated by various _____ which provide information about extracellular environment, DNA, or cell damage and whether each step in the cell-cycle has been properly completed
Inhibitory mechanisms
In cancers a lot of the cell cycle control mechanisms are:
Overridden
G0 state represents a :
Resting state or quiescent state
Cells can remain in G0 phase for:
Days to weeks or longer before resuming proliferation
Cells can enter C0 phase:
Permanently until they die
Cells enter G0 from a cell-cycle checkpoint in the:
G1 phase
G0 entry usually occurs due to;
Lack of growth factors or nutrients
G0 also occurs in cells when they reach:
Maturity
An example of maturity of a cell that enters G0 could be when the cell becomes:
Terminally differentiated
Examples of terminally differentiated cells:
Nerves cells
Heart muscle cells
Bone osteocytes
The dREAM complex forms and leads to ______ which leads to _____.
Histone compaction; suppression of gene expression
The dREAM complex puts cells into a dream state where they sit there and do nothing but:
Metabolize
The dREAM complex binds exclusively to:
Deacetylated histone H4
The dREAM complex is induced by _____ resulting in the compaction of the DNA in those regions
Histone modifications
The dREAM complex moves genes from a _____ state to a ____ state.
Euchromatin state to heterochromatin state
Protein (enzyme) that phosphorylates a target protein or another molecule
Kinase
Protein (enzyme) that removes a phosphate moiety from a protein or another molecule
Phophatase
Family of protein kinases involved in the control of the cell cycle:
Cyclin-dependent kinases (CDKS)
Family of proteins that regulate CDK activity
Cyclins
Regulatory transitions in the cell-cycle in which the cell cycle will arrested unless specific prior biochemical events are fully completed.
Checkpoints
Cell-division-cycle genes; important in cell-cycle checkpoint control
CDC
CDC-activating kinase
CAK
CDK inhibitor protein
CKI
Anaphase promoting complex or cyclosome
APC/C
CDK inhibitor protein
CKI
Ubiquitin ligase involves in cell-cycle control; named after its three subunits:
SCF
Origin recognition complex: protein complex bound to origin of replication sites in DNA
ORC
Complex of proteins involved in cell cycle control arrest and senescence by binding to the E2F family of transcription factors:
dREAM
Retinoblastoma protein: involved in cell cycle regulation
Rb
Genes that turn on and off dependent upon cures from environment, hormones, etc, that need to be present in the cell
Inducible gene expression
Genes that are expressed at a constant level throughout the life of a cell
Constitutive gene expression
