Apoptosis and Cancer Cells Flashcards
What sequence do caspases cut at
Aspartic acid followed by a alanine or serine residue
What are the executioner caspases
7, 3, 6
What are the regulatory caspases
9 (8, 10, 2)
What are the ICE Subfamily of inflammatory capases
1, 4, 5
What inhibits the activation of caspases
The anti-apoptotic bcl-2 family –> because they inhibit the apoptotic proteins hence prevent the release of cytochrome c
What are the different domains of Apaf-1
Outer Domain (C-terminal) --> contains the Cytochrome C binding domain Inner Domain (N-Terminal) --> contains the oligomerisation domain and the Caspase Recruitment Domain
What caspase does Apaf-1 recruit
Caspase 9
What are the two TSG where APaf-1 is shown to act as a TSG
HNPCC
Metastatic melanoma –> loss of heterozygosity and methylation of the remaining allele in 40% of metastic melanomas
What 2 ways do bcl-2 protect against apoptosis
1) Form ion channels in biological membranes
2) Bind pro-apoptotic proteins into the hydrophobic groove formed by the BH1-3 domains
What are the 2 helices that form the pore in BCl-2
5 & 6
How many forms of BCL-Xl are there
2
a) BCL-XL - anti-apoptotic (has BH4 domain) –> generally found in differentiated cells
b) BCL-Xs - pro-apoptotic (lacks BH4 domain)
Where are the two different distributions of bcl-2 and bcl-xl
bcl-2 –> found in proliferative bases of colonic crpts
bcl-xl –> expressed in the upper post mitotic regions
Name the ways in which the pro-apoptotic activity of BH3 proteins is regulated
1) Transcriptional activation and silencing
2) Stability and translation of the mRNA
3) Protein stability
4) Post translational modifications
5) Confirmational activation
6) Subcellular localisation and sequestration
How does stability and translation affect the activity of BH3 proteins
Bim mRNA stability is regulated by an AU-rich region in the 3’ UTR
Also miR17-92 inhibits mRNA translation of Bim
How does phossphorylation affect bad
Bad phosphorylation inactivates it
How does confirmational activity affect the activity of BH3 only proteins
MAP-1 = BH3 only protein, BH3 domain hidden inside mlecule through intramolecular interactions –> only exposed upon death receptor signalling
Loss of which 2 BH3 proteins has no effect on development
Puma and Noxa
What is the effect of Bid loss on tunorigenesis in mice
Get a CLL like lesion
What is the link between BH3 proteins and RA
Accumulation of inflammatory cells in the joints –> may be due to impaired apopotosis
Increased levels of bcl-2 seen in synciovytes
BH3 - only proteins have been shown to protect against RA in mice models
