Apoptosis Flashcards
nuc-1
Nuclease abnormal, DNA positive pyknotic bodies observed, mutant defective in DNA endonucleolytic activity
Ced-1 and ced-2
Cell death abnormal, defects in engulfment, ced1 encodes receptor on neighbouring cells, mutants used in subsequent mutant screens
Ced-3
LOF mutant -> all 131 cells fated to die survive, found homologous to interleukin 1B converting enzyme (ICE), caspase-1. Identified in ced-1 mutant screen - no cell corpses seen, therefore activity of CED3 is needed for PCD
Egl-1
Egg laying defective 1, GOF mutant, HSN neurons innervating vulva die, found to be a small BH3 only protein (proapoptotic)
Ced-3;egl-1 double mutant
HSN present as PCD not possible therefore egg laying restored, use of egl-1 mutant for suppressor screen suggested
Ced-4
Found in egg laying defect suppressor screen, similar phenotype to ced3; proapoptotic, similar to Apaf1
Ced-9
GOF mutation protects against PCD, first antiapoptotic protein found, involved in life or death decision, similar to Bcl-2, loss of function induces PCD
What does the misexpression of Bcl-2 cause.
Follicular lymphoma, B cells do not die, due to chromosomal translocation of chr14 and 18
What is the core pathway of PCD in c elegans
EGL1 -| CED-9 -| CED-4 -> CED-3 -> PCD
process can be reconstituted with only these 4 proteins
Can CED-3 alone cause processing of itself?
Yes but v slowly, active site cysteine mutant is totally inactive
What happens to the percentage of CED3 cleaved if we increase amount of CED4
Increases
What happens if we increase CED9
Blocks CED-3 in presence of CED-4
What does an increase in the BH3 only protein EGL-1 result in?
activates CED-3 by binding to CED-9 and preventing its interaction with CED-4, which can go off and cleave ced-3 zymogen
Physical interactions in PCD core pathway
EGL1 physically interacts with CED9
CED9 with CED4
CED4 with CED3
List the effector caspases
3, 7, 6