Term
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Definition
| Binds to DNA for fluorescent activated cell sorters |
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Term
| Distribution of cell cycles in FACS |
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Definition
| Most in G1; some in G2 and S; Sub-G1 is going through apoptosis |
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Term
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Definition
| Terminal deoxyribonucleotidyl transferase: catalyzes the addition of dUTP at the points of fragmentation, which can be seen (Tunel) |
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Term
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Definition
Annexin V protein has a strong, specific affinity for PS (usually on the inside of the cell, moves to the outside before apoptosis), and allows detected of apoptotic cells by
immunostaining or FACS analysis |
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Term
| Apoptosis: ATM/ATR, role? |
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Definition
1. ATM/ATR will detect this damage and
stimulate phosphorylation of Chk1/2 2.ATM can phosphorylate and stabilize p53 (also through the inactivation of
Mdm2) |
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Term
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Definition
| Chk1/2, which will phosphorylate (and inactivate) Cdc25 to mediate CDK inactivation. |
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Term
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Definition
The stabilized p53 transcription factor can stimulate transcription of CDKIs such as p21CIP1 to growth arrest the damaged cell, while DNA repair mechanisms can function to repair the damage. Once the damage is
repaired, the temporary growth arrest would be lifted. However, if the damage is too severe, p53 can also
stimulate apoptosis by inducing certain pro-apoptotic regulators (Bax) |
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Term
| Growth arrest or DNA repair |
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Definition
| At low levels of damage or stress, only a small amount of p53 is induced and/or stabilized. This low level of p53 will cause transcription of the genes associated with growth arrest, and DNA repair. / If however the damage or stress is acute or severe, this will lead to higher levels of p53 in the cell. This high level of p53 will promote the apoptotic process, and the ultimate elimination of the damaged cell from the general population. |
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Term
| Cell survival and growth factors |
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Definition
| Cell survival often depends upon the continued presence of growth factors (GF) or cytokines. If the stimulus is removed, it may initiate apoptosis |
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Term
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Definition
| Activation of the PI-3 kinase-Protein Kinase B (PKB) pathway leads to the phosphorylation of the pro-apoptotic Bad protein in the cytosol. Phosphorylated Bad is sequestered in the cytosol by a family of proteins referred to as 14-3-3. This prevents Bad from functioning at the mitochondrial membrane and initiating apoptosis through effector caspaces. |
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Term
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Definition
| Bad is not phosphorylated and does not interact with 14-3-3. Bad can interact at the mitochondrial membrane. Bad will inhibit anti-apoptotic Bcl-2 and Bcl-XL proteins, allowing the release of cytochrome C from the mitochondria. |
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Term
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Definition
| anti-apoptoic proteins inhibited by active Bad |
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Term
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Definition
| Cytochrome C and Apaf-1 will stimulate the caspace cascade and apoptosis. |
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Term
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Definition
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Term
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Definition
| Tumor Necrosis Factor Receptor (TNFR) |
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Term
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Definition
| Natural Killer (NK) cells and cytotoxic Tlymphocytes. |
|
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Term
| FasL: triggers apoptosis in who? |
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Definition
| FasL triggers apoptosis in virally-infected cells, in tumor cells, or in foreign graft-rejected cells. |
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Term
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Definition
| FasL binds to its receptor (Fas, or CD95), promoting the formation of a ligated homotrimer complex. FADD (or Fas Associated Death Domain) binds to the intracellular domain of the ligated receptor, and recruits and activates the effector Caspace 8, initiating the caspace cascade and apoptosis. |
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Term
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Definition
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Term
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Definition
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Term
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Definition
TNFα binds to its receptor TNFR and promotes formation of a ligated
homotrimer complex. TRADD (TNF Receptor Associated Death Domain) binds to the intracellular domain of the ligated receptor, and recruits FADD. FADD then activates the effector Caspace 8, initiating the caspace cascade and apoptosis. |
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Term
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Definition
| Conversely, TRADD can instead associate with an adapter protein that signals survival through the IkB/NFkB signaling pathway. |
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Term
|
Definition
| cytotoxic T-cells can also stimulate apoptosis through the proteins |
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Term
| Cytotoxic T-cell killing: Which MHC receptor? |
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Definition
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Term
| Cytotoxic T-cell killing: Enzymes used? |
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Definition
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Term
| Perforin and Granzyme mechanism? |
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Definition
| Granzyme B enters the target cell through the transmembrane pore-forming action of Perforin. Alternately, Granzyme B and Perforin enter the cell in endosomes, and Perforin promotes Granzyme B release into the cytosol. |
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Term
| Granzyme B, weapon of choice? |
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Definition
| Granzyme B promotes effector Caspace activation and apoptosis. This mechanism bypasses the normal control of apoptosis through pro- and anti-apoptotic regulator proteins, and instead directly activates the effector Caspase cascade inside the target cell. |
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Term
| Anti-Spoptotic proteins (2) |
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Definition
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Term
|
Definition
| Bim, Bid, Bad, Noxa, Puma |
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Term
| Mechanism of Pro-apoptotic proteins |
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Definition
| Proapoptotic proteins will increase the membrane permeability, facilitating the release of Cytochrome C (Cyto C) into the cytosol. |
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Term
| Mechanism of anti-apoptotic proteins |
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Definition
Anti- apoptotic proteins will decrease membrane permeability, and prevent the release of Cyto
C. |
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Term
| Cytochrome C and apoptosis |
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Definition
| Cyto C interacts with Apaf-1 in the cytosol and activates the Caspase cascade and apoptosis. |
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Term
| Inhibitors of Apoptosis Proteins (IAPs) |
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Definition
Restrain both initiator and effector
Caspases. They bind Caspases and inhibit their protease activities.
IAPs are found in the cytosol, and are present to prevent a slight and accidental release of Cyto C from inappropriately initiating apoptosis. |
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Term
| SMAC (Second Mitochondria-derived Activator of Caspases, also referred to as DIABLO) |
|
Definition
| released into the cytosol from the mitochondria, either during injury or in response to pro-apoptotic signals. SMAC inhibits the IAPs, there by promoting apoptosis. |
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Term
| Bcl-2, SMAC, Bid, Bim, and Cyto C |
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Definition
| anti-apoptotic Bcl-2 inhibits the release of both SMAC and Cyto C from the mitochondria, whereas Bid and Bim (like Bad) inhibit Bcl-2. |
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Term
|
Definition
| Forkhead transcribes CD95L (FasL) |
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Term
|
Definition
PKB (AKT) can phosphorylate and sequester the Forkhead TF...PKB
would prevent the activation of the Fas death receptor...PKB can phosphorylate and sequester Bad,
preventing the inhibition of Bcl-2, thereby decreasing the permeability of the mitochondrial membrane. Finally, PKB can phosphorylate and activate the IkB/NFkB signaling pathway, which leads to transcription of target genes for survival properties. |
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Term
| Inactive Apaf1 in cytosol... what happens? |
|
Definition
Apaf1 is an inactive monomer
bound with dATP. Cytosolic
Cyto C binds to and activates Apaf1.
The dATP is hydrolyzed leading to the
oligomerization of a seven-subunit
apoptosome complex. |
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Term
| Inactive caspases... what next? |
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Definition
| The initiator ProCaspase 9 binds to the active apoptosome. This leads to the autocleavage of ProCaspase 9, and its dimerization into active Caspase 9. Caspase 9 is referred to as an initiator Caspase, because it then cleaves the inactive effector ProCaspase 3 into the active Caspase 3. |
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Term
| signaling, regulation and execution of the apoptotic cascade (The very first step) |
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Definition
| p53 levels increase, leading to increased expression of Bax. Bax inhibits Bcl-2/Bcl-XL and causes the release of Cyto C from the mitochondria. Cyto C and Apaf1 activate the apoptosome, and the initiator Caspase 9. Caspase 9 can activate the effector Caspase 3. |
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Term
| signaling, regulation and execution of the apoptotic cascade (stopping the anti-death hippies) |
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Definition
| SMAC/DIABLO is also released from the mitochondria inhibiting the IAPs in the cytosol. |
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Term
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Definition
can become activated from Fas/FasL death receptor signaling / Caspase 8 can also cleave ProCaspase 3 to activate
Caspase 3. Active initiator Caspase 8 can also cleaves and activate Pro-apoptotic Bid |
|
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Term
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Definition
| like Bad, can stimulate Cyto C release from mitochondria |
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Term
| DNA fragmentation occurs when... |
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Definition
| Caspase 3 cleaves and inactivates PARP (Poly ADPribose polymerase), an enzyme involved in DNA repair and chromatin structure |
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Term
| Nuclear membrane breakdown occurs when... |
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Definition
| Caspase 3 (or Caspase 6) cleaves and inactivates nuclear lamins, which are involved in nuclear membrane structure |
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Term
| Additional pro-apoptotic signaling occurs at the mitochondrial membrane when... |
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Definition
| Caspase 8 cleaves and activates Bid |
|
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Term
| additional DNA fragmentation occurs when... |
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Definition
| Caspase 3 cleaves and inactivates ICAD, which normally functions to inactivate a Caspase 3-dependent DNAse |
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Term
|
Definition
| sugarbinding proteins, found in the macrophage can interact with glycoproteins and glycolipids found in the membrane of the apoptotic cell |
|
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Term
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Definition
| Anti-angiogenic factor, which also plays a role in expression of FasL. As a result, TSP can also serve as a link between the apoptotic cell (expressing TSP-binding sites) and integrins (expressed by the macrophage) |
|
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Term
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Definition
| (Intracellular Adhesion Molecule-3) is a glycoprotein that can interact with CD14 receptor in the macrophage. |
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Term
| B-cell follicular lymphomas |
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Definition
| A translocation between chromosomes 18q21 (containing the normal Bcl-2 locus) and 14q32 / juxtaposes Bcl-2 with an Ig heavy chain enhancer |
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Term
| Viruses and apoptotic processes |
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Definition
| inhibit Caspase activity, or mimic Bcl-2 activity. IAP-like proteins have been identified in bacculovirus to suppress apoptosis. |
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Term
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Definition
| inactivates p53 to suppress transcription of pro-apoptotic proteins |
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Term
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Definition
| binds to and inactivates Rb |
|
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Term
| Human papilloma virus (HPV) expresses two proteins |
|
Definition
| E6 and E7, which inactivate p53 and Rb, respectively |
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Term
| Aggressive strains of HPV |
|
Definition
| (16 and 18) / anal, vulvar, vaginal and penile cancers |
|
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Term
|
Definition
| Genital warts is caused by less aggressive HPV strains (6 and 11). As such, Gardasil was produced as a drug to helps prevent infections from these four HPV strains |
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Term
| stress and hypoxia in cardiac muscle cells from cardiac ischemia causes an increase in the active forms of... |
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Definition
| Caspase 9 and the effector Caspase 3 (compare the control and Ischemia β-gal lanes). This suggests that apoptosis is induced by cardiac ischemia, and provides a mechanism for cardiac muscle damage. |
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Term
| Treatment for apoptotsis via hypoxia |
|
Definition
| If the amino acid Tuarine is added to the system, the levels of active Caspases is comparable to nonhypoxic controls. Finally, if a dominant negative (inactive) form of AKT (PKB) was expressed, the beneficial effects of Tuarine are decreased. This suggests that Tuarine induces PKB activity to promote survival, even during hypoxia. |
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