L1.Cell Cycle Flashcards
When, in the cell cycle, does transcription occur?
Interphase. In G0 rates of transcription and translation very low.
When does a cell go into G0?
When environment doesn’t have an adequate supply of nutrients.
What happens during Prometaphase?
Chromosomes attach to mitotic spindles as telomeres move to the poles.
What structures seperate in anaphase?
Sister chromatids
Approximately how long does mitosis take?
~1 hr
What is required for a cell to pass the G1 checkpoint of the cell cycle? What are the options for a cell at G1 checkpoint?
- Adequate size
- Favorable env’t (nutrients and growth factors)
- Cells can proceed into the S phase. wait until reach proper size or proper environmental conditions arise, or they can go into G0.
What is required for a cell to pass the G2 checkpoint of the cell cycle?
- Adequate size
2. DNA must be replicated and DNA damage must be repaired
What is required for a cell to pass the mitosis checkpoint of the cell cycle?
- Chromosomes must be attached to spindle at the center before anaphase can proceed.
Cdks?
Cyclin dependent kinases. Protein kinases that play major role in controlling the cell cycle.
-Dependent upon cyclin protein associations
Cyclins?
Cyclin proteins activate Cdks so they can trigger different parts of the cell cycle.
-Different cyclins appear at different parts of the cell cycle
When cyclin intitially binds Cdk, an inactive cyclin-Cdk complex is formed. What two steps have to happen to activate the cyclin-Cdk complex?
Activation = Phosphorylation/Dephosporylation
- Protein KINASES phosphorylate the Cdk in two areas with one activator phosphate and one inhibitory phosphate.
- An activating protein PHOSPHATASE then must remove the deactivating phosphate.
A major part of cell cycle regulation is the abrupt breakdown of cyclins as the cell enters the M phase (cyclical proteolysis). How is this done?
Inhibition = Ubiquitinylation Process
- APC/C, a ubiquitin ligase, ubiquitinylates the cyclin.
- 26S Proteasome breaks down ubiquitinylated cyclins resulting in a deactivated Cdk.
What are the 4 cyclin-Cdk complexes and where in the cell cycle do they happen?
Cascade started by favorable environment 1. G1-Cdk; start of G1 phase 2. G1/S-Cdk; End of G1 entering S Phase 3. S-Cdk; S and G2 phases 4. M-Cdk; Entering M phase Cascade ended by ubiquitin ligase APC/C
What four factors stop the cell cycle? Where in cell cycle does each occur?
- Lack of Growth Factors; Beginning of G1 (also throughout)
- DNA Damage; G1-S, S, and M phases
- Unreplicated DNA; M phase
- Chromosomes not attached to spindle; b/t metaphase and anaphase of Mitosis. APC/C controls this.
After cell differentiation does cell division continue? Example? Exception?
No. differentiated cells never divide again. Ex. Myoblasts proliferate in myocytes and incorporate into tissues. Would be messy if they continued to differentiate. Exception = some differentiated cancer cells.
Growth factors are proteins that act locally by autocrine or paracrine signalling mechanisms. How do they pass signal along?
Growth factors can’t cross cellular membranes so they bind to membrane receptors, activating signal transduction systems that alter gene expression.
PDGF?
Platelet-Derived Growth Factor. A mitogen (induces mitosis) involved in mesenchymal cell division; wound repair.
EGF?
Endothelial Growth Factor. A mitogen (induces mitosis) involved in epidermal cell division; tooth differentiation.
TGFbeta?
Transforming Growth Factor beta. Osteoblast division; Chondrocyte differentiation
BMPs?
Bone Morphogenetic Proteins. Bone Cartilage and tooth differentiation. No cell division induction.
Induce ectopic bone formation by inducing pre-osteogenic cells to differentiate.
FGF?
Fibroblast growth factor. A mitogen (induces mitosis) Mesenchymal Cell division and differentiation.
Describe the signaling process induced by mitogens that results in the activation of Immediate Early Genes? (approximately 7 steps)
- Mitogens bind to membrane Receptor Tyrosine Kinase, which dimerizes and the tyrosine kinases autophosphorylate the cytoplasmic side of the receptor.
- Relay/adaptor proteins bind to Receptor Tyrosine Kinase and activate Ras Activating Protein.
- Ras Activating Protein facilitates a switch of GTP for GDP on the membrane bound Ras protein, activating it.
- Active Ras protein starts the MAP Kinase cascade by activating MAP kinase kinase kinase.
- MAP Kinase Kinase Kinase phosphorylates MAP KK, which phosphorylates MAP Kinase.
- MAP Kinases phosphorylate some proteins directly and phosphorylates transcription factors to effect gene expression.
- Transcription factor cause increased expression of Immediate Early Genes.
Which immediate early gene is responsible for the increased transcription of the delayed response gene G1 CYCLIN?
Myc
Note: Myc mutations exist in 70% of all human cancers! Very strong Oncogene if mutated.
What role role does the G1-Cdk complex play in activating transcription of G1/S cyclins and S cyclins?
G1-Cdk complex inactivates Rb protein, which, when active, binds to E2F transcription factor protein, inactivating it. Thus, when G1-Cdk inactivates the Rb protein, E2F is released and activated. E2F transcription factor induces the increased transcription of G1/S & S cyclins. Pushing the cell cycle forward.
