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31 Cards in this Set

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define apoptosis
a specific type of programmed cell death
that occurs by set pathways
and has set characteristics
(controlled and normal in development)
species where much apoptosis research was done?
C. elegans
Nematode worm contains 959 cells
symptoms of apoptosis?
cell shrinkage
cytoskeleton collapse
nuclear envelope breakdown (lamins)
chromatin breakdown
changes in cell surface
Where does Caspase get its name from?
C = cystiene (at active site)
asp = aspartic acid
ase = enzyme
What is a Caspase?
an inactive PROCASPASE
need cleaving to become active
two classes of caspase?
Initiator = cleaves other caspase's
Executioner (effector) = cleaves other Caspases AND target other protein cells
Extrinsic apoptosis?
Killer Lymphocytes
have ligand which binds with cells death receptor
actives caspases
Intrinsic apoptosis?
release of proteins from Mcd

Mcd? Random! Explain...
healthy Mcd retain their proteins.
Apoptotic Mcd release their contents into the cell.
Cyctochrome C is your protein (normally found in inter-membrane space)
what else is cytochrome c used for?
Cellular respiration... electron transporter in the ETC
Intrinsic apoptosis. The dets?
activation of apaf1 (apoptotic protease activating factor) by chromosome c
formation of CARD (Caspase Recruitment Domain)
recruitment and activation of PROCASPASE 9
Cleavage and activation of Caspase cascade
Step 1 Signal Transduction in Apoptosis?
Inactive BH123 aggregate in Mcd membrane and form pore to release proteins
Regulation of Step 1 Signal Transduction in Apoptosis?
1= Bcl2 protein prevents aggregation of BH123.

2= BH3 inactivates Bcl2 and triggers aggregation
What activates BH3?
Many signals but one is...
p53

Oh yea, whats that again?
p53 is a transcription factor
important during DNA repair
but you know that
how does p53 work?
it binds p21 gene
p21 gene encode a CKI, a Cdk Inhibitor protein.
This CKI then inactivates Cyclin and blocks the cell cycle.
But how does that help with apoptosis?
it also binds gene for BH3 protein. Ba-jingo!
2 properties of cancer
1- cells REPRODUCE in defiance of cell cycle controls
2- cells INVADE and colonise territories normally reserved for other cells
Benign?
Only uncontrolled cell division
(not yet invasive)
Malignant?
acquire the ability to invade surrounding tissue.
Leaves the lumen and breaks through the basal lamina
Metastases?
Secondary tumors due to primary being malignant.
what % of cancer is lifestyle or environment related?
80%
% of deaths related to cigarette smoking?
25% of all cancer deaths
3 ways a cancer can develop, i.e defeat cells growth mechanisms?
1- Hereditary disposition
2- mutation
3- viruses
name two oncogenes
Ras - signals the MAP kinase cascade
Myc - a regulator gene that codes for a transcription factor
Both are in the G1 cyclin production pathway
what is an oncogene
a gene that has the potential to cause cancer.
In tumor cells, they are often mutated or expressed at high levels
upregulated?
An increase of a cellular component is called upregulation
recap what p53 does
activated p53 binds the p21 gene which encodes the CKI
This CKI inactivates cyclins and blocks the cell cycle
excessive production of Myc
leads to transcription of Arf
Arf inactivates the Mdm2
Mdm2 is a negative regulator of the p53 tumor suppressor
leads to an active p53 protein

Need other mutation to cause cancer
what is Rb's role
Rb (retinoblastoma) is a tumor suppression gene and protein
Cell cycle needs E2F transcription factor.
Activation of E2F requires inactivation of Rb
most important tumor suppressor gene?
p53
is a transcription factor for
1- DNA repair
2- cell cycle control
3- apoptosis
the loss of p53 promotes cancer in 4 different ways...
1- cells with damaged DNA can continue to divide
2- cells with damaged DNA can escape apoptosis
leads to....
3- allowing division in cells with damaged chromosomes , promoting genetic instability and FURTHER MUTATIONS to occur
4-makes cancer more resistant to anti-cancer drugs
HPV?
Human PAPILLOMAvirus

causes cervical cancer

a fucken virus!
How does HPV work?
Jams the accelerator: inactivate the Rb protein which then cant inhibit E2F (promotes cell division cycle)
Kills the brakes: Inactivates p53, blocking tumor suppression