Cell Cycle, Cancer, and Cell Death Flashcards
What are the 5 phases of the mitosis phase of the cell cycle?
Prophase Prometaphase Metaphase Anaphase Telophase
Describe what happens in the prophase of the cell cycle.
The cell begins to assemble the mitotic spindle, a set of microtubules extending from the centromeres which will later attach to the chromosomes.
Describe what happens in prometaphase of the cell cycle.
The nuclear envelop disintegrates and the microtubules of the mitotic spindle attach to the chromosomes.
Describe what happens in metaphase of the cell cycle.
The chromosomes are aligned in the mitotic spindle. There is a pause here to allow all chromosomes to become attached.
Describe what happens in anaphase of the cell cycle.
The cohesion proteins which bind the sister chromatids together are cleaved and the chromosomes are pulled apart by the mitotic spindle.
Describe what happens in telophase of the cell cycle.
The nuclear membrane reconstitutes around each set of chromosomes.
What are the 4 stages of the cell cycle? Where does Go fall?
Mitosis -> G1 -> S -> G2 -> Back to M Phase
Go is between M phase and G1
Describe the function of each phase of the cell cycle.
M Phase- Mitosis
Go- Quiescent, non-cycling
G1- duration between the completion of cell division and initiation of DNA replication where the cells start to build mass
S Phase (synthesis)- DNA Replication
G2 Phase- duration between the completion of DNA replication and initiation of cellular division
Distinguish between progression and transition in terms of the cell cycle.
Progression- going through the cell cycle phase
Transition- from one phase to another
What are the 3 main cell cycle regulators?
Cyclins
Cyclin Dependent Kinases (CDKs)
Cyclin Dependent Kinase Inhibitors (CKIs)
What are the 4 types of cyclins?
G1- Cyclins C, D1-2, E1-2, F, and G
S- Cyclin A
G2/M- Cyclins B1-2
Cyclin H- constitutive expression
What are the 3 types of CDKs? What do they bind with?
CDK4/CDK6 binds with Cyclin D (G1)
CDK2 binds with Cyclin E (G1) and Cyclin A (S)
CDK1 binds with Cyclin B (G2/M)
What are the 2 types of Cyclin dependent Kinase Inhibitors?
INK4 families
Cip/Kip families
T/F Cyclin expression level rises and falls, but their activity level remains constant. CDK expression levels are always constant, but their activity levels rise and fall.
True
In order to turn CDK/Cyclin complex off, which one gets ubiquitinated?
Cyclin, this is why their expression level rises and falls
Describe the activation of the CDK-Cyclin complex.
CDKs have T Loop sites that can be phosphorylated. Phosphorylation of the T Loop site activates the CDK-cyclin complex, while phosphorylation on the roof site inactivates it.
For the complex to be active , therefore it must be phosphorylated on the T Loop site, but dephosphporylated on the roof site by the protein phosphatase cdc25.
What is the function of CDK1?
Triggers G2 -> M transition.
Cyclin A is synthesized in S and destroyed starting are prometaphase.
Cyclin B is synthesized is S/G2 and destroyed following the completion of chromosome attachment to the spindle.
What is the function of CDK2?
Triggers G1 -> S transition
What is the function of CD4/CDK6?
Phosphorylates retinoblastoma susceptibility protein (pRb) in G1. This triggers the passage of the restriction point and cyclin E synthesis in cells.
Extracellular growth factors control synthesis of D cyclins.
What is the function of CKIs?
When are they activated? How do they inhibit and what are the 2 main CKIs?
To block the action of CDKs and ensure tight control of the cell cycle.
They are activated upon cell cycle checkpoint activation.
Inhibit by binding to the CDK-Cyclin complex
2 Main CKIs are p21 and p27
What are Ras superfamily proteins also called?
Small G Proteins or Small GTPases
What is the function of Ras?
To control cell cycle entry and progression through the cell cycles.
Essentially stimulates the entry into S Phase
How does Ras control entry into the cell cycle and its progression?
Receptor activates Ras (an intracellular peripheral protein), which activates MAP Kinase. This activates promoters of the Myc gene in the nucleus. Myc upregulates Cyclin D gene (increases G1-CDK activation), which increases Rb phosphorylation, which increases E2F activity. Myc also directly increases the E2F gene, which increases entry into the S Phase.
*Rb stands for retinoblastoma protein.
What is the restriction point and in which phase of the cell cycle is this found?
what does it require to pass this point?
The restriction point is the point where cells commit to divide. No turning back after this point is reached.
It is found towards the end of G1 phase and requires Cyclin D and CDK4/6 to pass through.
What complex is required in order to pass from G1 to S phase? Explain how this process occurs.
E-CDK2 is required.
D-CDK4 phosphorylates pRb, which leads to E-CDK2 hyperphosphorylating pRb, which liberates the transcription factor E2F. E2F triggers an increase in the transcription of the cyclin E and E2F genes, which leads to the synthesis of more cyclin E and the formation of more E-CDK2, which drives more phosphorylation of pRb.
What complex is required in order to pass from G2 to M phase? Explain how this process occurs.
B-CDK1 is required.
cdc25 phosphorylates Cyclin-B CDK1 and allows it to translocate into the nucleus where it initiates the spindle assembly.
The spindle assembly formation leads to the activation of Anaphase Promoting Complex (APC), which then destroys CDK1 by ubiquitinating it and therefore freeing Cyclin B for degradation.
