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P53 Apoptosis Cancer History of Cancer
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P53
Apoptosis
Apoptosis
Apoptosis
is programmed cell death. It is a good way for a cell to die because it doesn't
explode like cells with viral infections, damaging cells around it, but rather
shrinks and collapses inward causing little damage to surrounding cells. This
is a normal part of tissue growth and occurs throughout our bodies. It is for
example, why we are born with distinct digits, instead of webbed hands or feet.
During development the skin cells that were between our fingers undergo
apoptosis, so that we can later enjoy free-moving fingers. Apoptosis also
occurs when a cell detects irreparable DNA damage. This is why apoptosis is an
important subject in the study of cancer. Why don't these obviously defective
cancer cells just tell themselves to die? Developing a therapy that would cause
cancer cell to undergo apoptosis may theoretically be a cure to all cancer. The
problem with this method is that apoptosis, like all cell processes, is
controlled by a complex process involving genes. The genetics of different
types of cancer is complex and unique. In spite of this, a large number of
cancers share a common mutation in genes involved in cell death, so the
understanding this process and its gene regulation will yield future cancer
therapies.
Mechanism of
apoptosis
There are 2 main types of how cell undergo
apoptosis. Though they partly share mechanisms, there is intristic apoptosis,
and extristic apoptosis.
Intristic Apoptosis
This
is also called the Mitochondrial pathway of apoptosis. It is initiated by
signals within the cell, usually involving an inability to repair DNA damage.
-several large proteins and enzymes bind to
caspase-9 forming the apoptosome .Caspases are proteases. Proteases hydrolyze
peptide bonds (chew up proteins and enzymes). Caspases specifically cleave proteins
after aspartic acids.
-The activation of caspase-9 activates other
caspases causing protolytic activity all throughout the cell.
- Structural proteins are digested in the cytoplasm
and DNA is degrated.
-Phagocytosis of cell occurs.
Extristic Apoptosis
This
is also called the Death Receptor pathway. It is initiated by external signals.
-Fas and TNF receptors are cell receptors that have
parts of themselves outside of the cell.
-The "death activators", FasL and TNF
bind, activate caspase 8.
-The rest of the cell death is the same as with
internal signaling. The caspase cascade degrades proteins and DNA until the
structure is ingested by a phagocyte.
Genes and
Apoptosis. P53; the connection between cancer and apoptosis.
Genes
involved in apoptosis are either pro-apoptotic (promote apoptosis) or
anti-apoptotic (inhibit apoptosis). P53 is a pro-apoptotic genes present in all
cells, but has special significance to cancer cells. It is a tumor repressor
gene, meaning that its presence reduces the occurrence of cancer tumors by
promoting apoptosis in cancer cells. Normally it induces apoptosis by
activating caspases 9, 8, 7, and 3. The loss of p53 decreases caspase
activation and therefore the cell will not undergo apoptosis. Mutation in the
p53 gene is the most common mutation in cancer; it is present in about half of
all cancer tumors, 80% in all colon cancer tumors, 50% of lung cancer tumors,
and 40% of breast cancer tumors.
Home Mitosis Meiosis
P53 Apoptosis Cancer History of Cancer
Treatments Transgenic Mice Dox Treatment Future of Dox Credits