Cell Cycle Control and Cell Division Flashcards
The entry into mitosis in the cell cycle is triggered by what?
M-CDK mediated phosphorylation of specific proteins, along with protein kinases (2 families)
How does G1-CDK activate the E2F proteins?
G1-CDK phosphorylates the Rb protein, releasing it from E2F
Which component of the cell-cycle control system detects whether or not the chromosomes are attached to their spindles?
APC/C
At what phase of the cell cycle are CDK4-cyclin D and CDK6-cyclin D active?
G1 phase
The SMAD proteins target ___ and ___ to prevent cell cycle progression by inhibiting the cyclins.
p21; p15
What does the cell cycle involve?
DNA replication and cell division to create two identical daughter cells
How is the cell cycle controlled by proteolysis?
- 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
___ signaling involves gene regulatory factors and ribosome synthesis to promote protein synthesis and cell growth.
m-TOR
The MAPK leads to the activation of what?
activation of immediate early gene expression (genes turned on immediately after a mitogen binds to the receptor)
Where is the second checkpoint?
at the end of G2, right before the M phase
Is there an intact nuclear envelope still present during prophase?
YES
TGF-B works through the ____ proteins.
SMAD
____ interact with cell surface receptors on the cell surface, which leads to the activation of a kinase.
Mitogens
At what phase is CDK2-cyclin A active?
middle of S phase
The ___ cyclin is the protein that binds to S-CDK and moves the cell through the S phase.
S
What part of the cyclin-CDK complex gets ubiquinylated?
cyclin
The activity of cyclin-CDK is further regulated by Wee1 kinase. What does Wee1 kinase do?
Wee1 further phosphorylates cyclin-CDK to render it inactive
What is the pathway of a mitogen-activated protein kinase (MAPK) signaling cascade?
stimulus»_space; MAPKKK»_space; MAPKK»_space; MAPK»_space; biological reponse
How does the division of the cytoplasm occur?
by contractile rings
What does the loss of CDKs mean after their inactivation?
M phase is completed (their targets can be dephosphorylated by various phosphatases present in anaphase)
What CKI helps cells withdraw from the cell cycle when they terminally differentiate?
p27
Why does p27 insert itself into the ATP-binding site of the cyclin-CDK complex?
to inhibit enzyme activity by preventing it from phosphorylating any targets
What complex initiates the metaphase-anaphase transition?
Anaphase-Promoting Complex (APC/C)
What kinase is primarily involved in suppressing CDK1 activity before mitosis by phosphorylating inhibitory sites?
Wee1 kinase
The metaphase-to-anaphase transition involves ___.
proteolysis
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
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
How many D cyclins are present in mammals?
3 (D1, D2, D3)
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
CDK requires the binding of ___ and ___ to become an active enzyme.
cyclin; subsequent specific phosphorylation
What are the partners of the G1-CDK complex?
cyclin D and CDK4, CDK6
What does the degradation of securin lead to?
the activation of a protease that separates the sister chromatids and unleashes anaphase
What tags the cyclin-CDK complex for degradation?
binding of many ubiquitin molecules to the cyclin by ubiquitylation enzymes
What are the two critical proteins that initiate the formation of the pre-replicative complex?
CDC6 and CDT1
What is CDT1 inhibited by?
geminin
What is cancer?
inappropriate proliferation
___ can phosphorylate the T-loop at a threonine residue in the T-loop and fully activate the cyclin-CDK complex.
CDK-activating kinase (CAK)
The accumulation of the S-CDK concentration initiates the degradation of ____.
phosphorylated CDC6
___ activates APC/C and maintains its activity through G1. It is inhibited by CDK activity.
CDH1
The activation of ___ triggers the events of mitosis, which includes chromosome segregation.
M-CDK
____ starts abruptly with the breakdown of the nuclear envelope. Chromosomes can now attach to spindle microtubules by their kinetochores.
Prometaphase
At what phase is CDK2-cyclin E active?
end of G1 phase
When does mitosis begin?
after the G2/M checkpoint has insured that all of the DNA has been replicated correctly
The ___ cyclin is the protein that moves the cell cycle forward from G1 to S.
G1/S
The initiation phase of DNA replication is divided into 2 steps. What are they?
- Late mitosis-early G1
- Onset of S phase
Once E2F proteins are released and activated, it drives the formation and synthesis of ____.
C-cyclins and S-CDK
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)
Which complex assesses whether or not the cellular environment is favorable?
G1-CDK
In what phase is the pre-replicative complex disassembled?
S phase
The ____ stimulate cell division mainly by stimulating G1/S-CDK activity that inhibits intracellular negative controls.
mitogens
What are the critical determinants of cancer progression in the cell cycle?
genes involved in cell-cycle regulation and control
What is the S phase?
where DNA is replicated
When abrupt increase of activity drives entry into mitosis?
M-CDK
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
The dREAM complex puts itself into which phase of the cell cycle?
G0
What are the partners of the G1/S-CDK complex?
cyclin E and CDK2
What is the M phase?
where cells divide
___ induces the assembly of the mitotic spindle, chromosome condensation, breakdown of the nuclear envelope, and rearranges the actin cytoskeleton and Golgi.
M-CDK
What are the two sister chromatids held together by?
kinetochores
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
At each checkpoint, the main cyclin increases in concentration and then decreases as the next phase’s cyclin ___ in concentration.
increases
Where is APC/C activated at?
in mid-mitosis
___ 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
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
Activation of cyclin-CDK is a prerequisite for many downstream events. A mutation in any of these downstream, tight regulations can lead to ___.
cancer