Apoptosis Flashcards
Outline the role of BH3 only proteins?
regulated by transcriptional & post-translational mechanisms
sequestered by anti-apoptotic members.
mediate direct activation of Bax or Bak when activated or relieve anti-apoptotic antagonisms –> allows oligomerisation.
how can the extrinsic signal be amplified?
caspase 8 cleaves Bid which translocates to OMM inhibiting anti-apoptotic Bcl2 proteins.
What are the main targets for caspases?
PM Nucleus Cytoskeleton ECM detachment Genetics.
Which BCL-2 family member proteins are; apoptotic, anti-apoptotic and BH3 only
Bax or Bak
Bcl2 or BclXl
Bad, Bim, Bid, Puma, Noxa
How is the intracellular osmotic gradient maintained during apoptosis?
Transgluatminase is an intracellular enzyme linking glutamine to lysine covalently –> cross links proteins, membranes remain intact.
What is the first mechanism by which T cells can induce the death of their targets?
Fas-Ligand on killer cell surface
Binds TM receptor Fas on TARGET cell.
(targets can be B cells!)
How are apoptotic cells recognised?
Release chemoattractants e.g. lysophosphatidylcholine genrated from phosphatidylcholine by iPLA2 (activated by caspases) cleavage.
PS on cell surface (receptor to be identified -potentially extracellular thrombospondin)
What is the role of p53?
activates transcription of genes encoding PUMA & NOXA.
Briefly outline T cell development.
progenitors express V(D)J recombinase & rearrange TCR gene segments.
Express CD4 & 8 & interact with thymus dendritic cells expressing self-peptides bound to MHCI / II
High affinity binding undergo -ve selection
Inability to bind don’t receive signal & die
Correct binding +ve selection.
CD8 or 4 silenced by methylation.
Briefly outline necrosis.
severe or sudden injury
holes in PM - molecules leak into cell causing swelling
intracellular contents leak out (uric acid, HSPs, ssRNA)
Inflammatory response
cells disintegrate,
