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45 Cards in this Set
- Front
- Back
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intrinsic triggers of apoptosis?
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inappropriate DNA synthesis
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Extrinsic triggers of apoptosis
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CTL
NK cells Cytokines |
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why do some viruses perturb apoptosis?
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prevent premature cell death allow an increase in viral replicatoin
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why may viruses increase apoptosis?
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ensure efficient spread of the virus during lytic infection
evades the inflammatory response unlike necrosis |
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3 extracellular mechanisms of apoptosis?
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FAS ligand binding
TNFr Death domain proteins (FADD) |
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how does FAS trigger extrinsic apoptosis?
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interacts with fas ligand due to direct cell to cell contact
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how does TNFr trigger extrinsic apoptosis?
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soluable cytokines
TNF trimer binds to TNFr --> intracelular signalling Caspase activation Cell death |
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what are death domain proteins/
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have specific domains which interact with other death domain proteins
activate caspases, exonucleases, proteases lead to cell death |
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two proteins initiation intrinsic apoptosis
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P53
BCL-2 |
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4 viruses studied in apoptosis
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ADV = linear dsDNA
HPV-16 SV40 HBV |
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how is p523 turned over in normal cells?
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MDM-2 = ubiquitin ligase
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when are p53 levels increased?
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hypoxia
DNA damage STRESS |
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what effect do the different types of cellular stress have on p53?
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differential phosphorylation
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What is the first attempt of p53 when induced?
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stabilise DNA to allow for repair
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if DNA can not be repaired how does p53 initiate apoptosis
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binds Bax (pro-apoptotic)
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what does Rb phosphorylation lead to and when?
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at the end of G1 (P)Rb --> E2F dissociation and DNA replication
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what control mechanism is in place to prevent over activation of genes if Rb is lost?
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loss of Rb --> increased p53
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how do oncogenic viruses deregulate cell cycle?
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target both p53 and Rb
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HPV protein interacting with Rb
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HPV-16 E7
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HPV protein interacting with p53?
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HPV-16 E6
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how does HPV target p53 for proteolytic degradation via e6?
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induced E6AP binding to p53 --> ubiquitination
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Viral proteins which bind to and innactivate p53
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ADV - E1B
HPV - E6 SV40 - Large-T HBV - pX |
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Viral proteins which bind to and inactivate Rb
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ADV- E1a
HPV- E7 SV40 - large-T |
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What protein retains the MPTP closed?
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Bcl-2 (anti-apoptotic)
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PRotein opening the MPTP?
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BAx (pro-apoptotic)
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what does the opening of MPTP lead to?
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lost of membrane potential
Cytochrome C release Apoptosome formation Caspase activation DEATH |
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How do adenovirus, HSV, Vaccinia inhibit MPTP opeining?
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encode Bcl-2 homologues
no membrane potential loss ect |
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how does HCMV prevent apoptosis (mitochondrial)
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encodes an untranslated RNA in early infection
binds complex-I (NADH) prevents complex-I mediated apoptosis induction Rotenone- block HCMV |
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what is theER stress response triggered by?
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unfolded proteins in the ER
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ER stress response
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BiP recruitment --> re-folding of proteins
ATF6 cleavage from BiP --> moves to nucleus to up regulate transcription |
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What happens if the proteins are not folded correctly after induction of ER chaperones?
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UPR induction
Ca release Caspase 12 activation Apoptosis |
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how do viruses induce the UPR
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viral infection --> unfolded proteins in the ER due to replicaiton sites e.g. DEngue, HCV
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What is the role of PERK?
(part of ER stress response) |
bound by BiP
(P) eIF2alpha translational arrest allows re-folding |
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how does HCMV block the UPR
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blocks ATF6 cleavage and nuclear transloaction
no increase in UPR genes |
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how does TNFr cause extrinsic apoptosis?
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increases phospholipase movement to membrane
activates caspase-8 which cleaves procaspase-3 initiation cell death |
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What does binding of FAS-L cause?
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recruitment of other DD containing proteins
Apoptosis via caspase activation |
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which region of adenovirus expresses inhibitors of apoptosis?
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E3
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how does RID complex from adenovirus inhibit apoptosis?
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removal of Fas from the cell surface
no ligand binding |
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how does ADV 14.7K block apoptosis?
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inhibits caspas-8 activation
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how does KSHV inhibit extrinsic apoptosis?
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inhibits FADD
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what do viruses encode to prevent FADD mediated caspase activation?
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vFLIPS e.g. KSHV-K13
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what does cowpox virus encode to inhibit extrinsic apoptosis?
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CrmA - serine protease inhbitor
inhibits multiple caspases and granzyme B |
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how does TGF-B induce apoptosis?
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triggers TF activity switching on p21 which blocks cyclin dependant kinases induces apoptosis via G1 arrest
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how does latency avoid the immune system?
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only LATs are produced no proteins
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what is the function of LATs/
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protect the neurone from apoptosis by promoting degredation of pro-apoptotic TGF-b
DICER mediated |
