Cell Cycle Regulation Flashcards
Abnormal Cell Cycle Results:
- Inappropriate proliferation = [1]
- Enter S Phase with DNA dmaage = [2]
- Errant chromosome separation = [3]
- Errant cell growth = [4]
[1] cancer
[2] mutations in genome
[3] aneuploidy, cell death
[4] inappropriate organelle distribution
The CDK Complex: The Cell Cycle Machinery is [1] dependent. It is a kinase in nature, but it is inactivated unless it it paired with [1].
[1] Cyclin
[1] CDKIs inhibit kinase and catalytic activity regardless of the cell cycle checkpoint. Inhibition occurs WITH the cyclin as part of the complex.
[1] CIP/KIP
– note: these numbers are ABOVE the “teens” in number
[1] CDKIs only bind to G1 checkpoint CDKs (CDK4 or CDK6), displacing [2]
[1] INK4
– note: these numbers are IN the “teens”
– p16, p15, p18, p19
[2] Cyclin D
The CDK [1] is found at the Mid G1 checkpoint.
The Cyclin [2] is used.
[1] CDK4 or CDK6
[2] Cyclin D
The CDK [1] is found at the G1/S checkpoint.
The Cyclin [2] is used.
[1] CDK2
[2] Cyclin E
The CDK [1] is found at the S checkpoint.
The Cyclin [2] is used.
[1] CDK2
[2] Cyclin A
The CDK [1] is found at the G2/M checkpoint.
The Cyclin [2] is used.
[1] CDK1
[2] Cyclin A
We have a CDK4/6 and Cyclin D. We must be at the [1] checkpoint. This is a [2]-dependent stage.
[3] is the substrate for this checkpoint. It is normally active in the hypophosphorylated state. In this state, it sequesters [4].
[1] Mid G1
[2] growth factor
[3] Rb
[4] E2F
[1] is freed and initiates transcription at the G1 checkpoint. It starts producing [2] and more of itself to prepare for late G1 and S phase entry.
[1] E2F
[2] Cyclin E
S-Phase SCF Ubiquiting Proteolysis:
The G1 cyclin/CDK complex will phosphorylate, ubiquitinate, and destroy [2] attached to the S-phase cyclin/CDK complex. This allows this complex to start S phase and begin the DNA replication process.
[1] p27
G2-M Checkpoint - activating Mitotic Cyclins:
During mitosis, the cyclin [1] is in high concentration.
[2] will phosphorylate a tyrosine and INACTIVATE the B-CDK
[3] will phosphorylate the threonine with activating power, but the complex is still inactivated due to [2]
Finally, [4] will dephosphorylate at the tyrosine location to fully activate the B-CDK
[1] Cyclin B
[2] Wee1
[3] CAK
[4] Cdc25
The two replicated chromosomes are held together at the centromere by a protein called [1] and cohesin.
In anaphase a protein called [2] that is normally inhibited by [3] will cleave [1] and allow separation of the chromosome.
[1] Klesin
[2] Separase
[3] Securin
In anaphase, [1] complex targets [2] for ubiquitination-mediated degradation to free Separase.
[1] APC-Cdc20
[2] Securin
In G1, Cdh1 is [1] due to action from the G1 Cyclin CDK complex.
In anaphase, there is a Cdc14 phosphatase that is expressed that will activate Cdh1 with APC.
[1] phosphorylated (inactive)