regulation of cell number and cancer cells special limited edition packet tuesday, november 10,...
TRANSCRIPT
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Regulation of Cell Number and Cancer
CellsSpecial Limited Edition Packet
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There are intracellular and extra cellular signals that control the cell cycle and apoptosis.
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Intracellular Controls
Intracellular controls may either be “negative” controls or “positive” controls. Negative controls will stop either the cell cycle or
apoptosis Positive controls will promote either the cell cycle or
apoptosis.
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Cell CycleNegative Intra Cellular Controls
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Negative Intracellular Control I
DNA is damaged during the S phase
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Negative Intracellular Control I
p53 is activated and produces p53 protein.
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Negative Intracellular Control I
p53 protein becomes a transcription factor for p21 gene.
p21 is activated.
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Negative Intracellular Control I
p21 inhibitor protein is produced. This inhibitor protein is
an inhibitor of cyclin dependent kinase complexes. (CDK complexes)
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Negative Intracellular Control I
p21 inhibitor protein inhibits CDK complex and stops the complex from activating E2F when it phosphorylates the Rb protein.
When E2F is inactive, the cell cycle stops.
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Positive Intracellular Control
The Cell Cycle
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Positive Intracellular Control I
When the damaged DNA is repaired (details to come in DNA replication packet), the previously mentioned process is reversed.
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Positive Intracellular Control II
p53 becomes deactivated and reduces the amount of p53 proteins.
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Positive Intracellular Control II
p21 gene is turned off/does not turn on.
CDK complex is activated/reactivated.
Cell cycle re-starts.
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Positive Intracellular Control III
Additionally, independent signals from within, or outside, the cell produce a cascade of protein kinases. Initiates a
phosphorylation cascade.
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Positive Intracellular Control III
Ultimately, the CDK complex is phosphorylated and becomes active.
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Positive Intracellular Control III
Activated CDK complex phosphoroylates the Rb protein.
Rb protein is turned off.
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Positive Intracellular Control III
E2F protein is released from the Rb protein.
E2F becomes active.
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Positive Intracellular Control III
E2F becomes a transcription factor and binds on the S-phase genes.
The S-phase proceeds forward.
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Positive Intracellular Controls
Apoptosis
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Introduction—Apoptosis
It has been known for several years that many forms of cellular damage trigger leakage of mitochondria. Leakage of proteins from within the mitochondria.
This leakage indices the apoptotic response.
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Positive Intracellular Controls—Apoptosis
Cytochrome C, when leaked from the mitochondria, binds to an apoptotic protease activating factor (Apaf) to form the cytochrome c-Apaf complex.
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Positive Intracellular Controls—Apoptosis
The cytochrome c-Apaf complex activates the initiator capase. Capases are proteins
that behave as transcription factors and activate suicide genes. They activate
apoptosis.
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Negative Intracellular Controls
Apoptosis
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Introduction I
Once a capase becomes active, there is no way to stop apoptosis.
Therefore, mechanisms to prevent apoptosis from starting, under normal conditions, has been observed.
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Negative Intracellular Controls—Apoptosis
Bcl proteins block the release of cytochrome C from the mitochondria and has the ability to bind to Apaf and prevent the activation of the capases.
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Positive Extracellular Controls
The Cell Cycle
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Introduction
Cell division is promoted by the action of mitogens. Polypeptide ligands released from paracrine sources
within the immediate area.
Mitogens are also called growth factors.
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Mitogens
EGF (epidermal growth factor) activates RTK’s. RTK = tyrosine receptor kinase.
RTK initiates an intracellular transduction pathway described previously. CDK complex becomes phosphorylated and
becomes active…
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Negative Extracellular
ControlsThe Cell Cycle
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Introduction
Certain secreted proteins are known to inhibit cells from dividing. TGF-β
Transforming growth factor beta
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Negative Extracellular Controls I
TGF-β activates TGF-β receptor (a type of tyrosine kinase receptor).
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Negative Extracellular Controls I
SMAD proteins are phosphorylated. Phosphorylation
cascade.
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Negative Extracellular Controls I
CDK complex becomes phosphorylated.
Rb protein is turned on.
Rb protein binds to E2F…stopping the cell cycle.
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Positive Extracellular Controls I
Apoptosis
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Positive Extracellular Controls I
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