T1Q5: Apoptosis Flashcards
Leaning Objectives • understand necrosis vs. apoptosis • understand the steps in apoptosis, and the proteins involved at each step Key wh- what wy- why wn- when whr- where
necrosis
- wh
- wy
disordered death due to cell damage
apopotosis
ordered cell death
intrinsic pathway
wh: orderly cell suicide
wy: withdrawal of cytokines/ growth factor or due to damage from radiation/ free radcials
extrinsic pathway
wh: cell execution
wy: triggered by Fas/Fas-Ligand, used by Cytotoxic T-Cells
Apaf-1
sig: adaptor protein, associates with caspases and activates instrinsic cell death
def: pro-apoptotic protease activating factor 1
FADD
sig: activated Fas receptor associates with FADD as an adaptor molecule to transmit its signal inside the cell
def: fas associated protein with Death Domain
Blc-2
sig: REGULATORS of the intrinsic pathway. some are pro- others anti-
def:
1. breakpoint cluster locus-2 protein, a pro-survival protein expressed on the cytoplasmic leaflet of various membrane proteins
2. a family of proteins transmembrane proteins named after their founding member that either favor or prevent cell death
BH1-4
def: Bcl-2-homology, a conserved domain in Bcl-2 family of regulatory proteins.
sig:
survival regulatory factors contain BH1&2
Bcl-2 proper, Bcl-xL, and Bcl-w
pro-apoptotic:
Bax, Bac, and Bad- conain Bh1, BH2, Bh3
BH3
sig. found in several KILLER proteins that may play an antagonistic role to pro survival proteins
def. break-cluster 2 homology region
mechanism:
BCl2 anti-apoptoic proteins
(Bcl-2 proper, Bcl-xL, and Bcl-w)
anti-apopotic proteins bind to Apaf1 and prevent it from activating capase enzyme
They may also prevent the mitochondria from releasing cytochrome C complex
mechanism: BCL2 family
pro-apoptotic proteins
Bax, BAD, Bak and Bok
removal of pro-survival proteins from Apaf1
They may also promote liberation of cytochrome C from the mitochondrion
caspase
def: cysteine in active site, acts on aspartic acid residues
significance: Ced caspases activate apoptosis
initiating caspases
wh: Ced8 & Ced9 begin apoptosis by associating with adaptors
hw: aggregation and association with adaptor proteins (FADD or Apaf-1)
execution caspases
wh: Ced3, Ced6, Ced7 destroy things and activate things that destroy things
hw: activated by cleavage by initiating caspases and they go on to cleave substrates within the cell
CAD
wh: cytoplasmic DNAse (CAD)
wy: example of a protein that is selectively/ coordinately cleaved to produce targeted loss of function rather than indiscriminate damage
scramblase
flips phosphotidyl serine from its position in the inner cytoplasmic leaflet to the extracellular membrane
phosphatidyl serine
wh: pholipid in Plasma membrane
wy: “eat me” signal
CED1
a major receptor for phagocytosis of apoptotic cells (corpses)
Myc
wh: an oncogene (protective gene that when mutated can cause cancer)
wy: may initiate apoptosis if there is an absence of growth factors or genotoxic damage
p53
wh: an oncogene
wy: initiates apoptosis if cell damage occurs
dysregulated apoptosis: inhibition
cancer
dysregulated apoptosis: increased apoptosis
- neurodegenerative diseases (Alzheimer’s)
- ischemic injury: heart disease and stroke
- virus-induced lymphocyte depletion (AIDS)
Apaf-1 is to ___ as ____ is to Extrinsic Pathway
“adaptor” protein question
Apaf-1 is to the intrinsic pathway as FADD is to the Extrinsic Pathway
What two capases activate apoptosis?
Ced8 and Ced9
What three capsases execute apoptosis?
Ced 3,6,7