Exam 2 Flashcards
(118 cards)
apoptosis
programmed cell death
p53
homotetramer transcription factor for apoptosis genes and repair mechanisms (binds DNA and responds to stress/damage)
describe why it is important to know that p53 is a homotetramer
only 1/16 of all possible combos is functional because need all 4 WT and no mutation
why is it better to have the p53+/- genotype than the p53+/m
absent, phenotype is mostly normal but mutation, the phenotype is that there is no p53 function
p53 turns on what genes…
mdm2, cell cycle arrest genes (p21/27), DNA repair genes, apoptosis genes
stressors that can turn on p53
lack of nucleotides, UV radiation, ionizing radiation, oncogene signaling, hypoxia, blockage of transcription
why is it an advantage that p53 is constantly expressed in all cells all the time
energy consuming but beneficial because it allows rapid response to stress and a fast way to turn off proliferation
mdm2 function
regulates p53 via negative feedback
how does mdm2 regulate p53 via negative feedback
- lots of copies of p53
- some p53 P even when not stressed so p53 binds DNA—> translate Mdm2 protein
- Mdm2 then feeds back and initiates degradation of un-P p53 by ubiquitination
when is p53 P
stress
how is was signaling involved in p53 expression and function
GF–> Ras–> Mapk/Erk1/2 —> proliferation
overaction GF/Ras signaling will increase Mdm2 expression so there will be very little or no p53 and no regulation
how can we prevent the consequence of overactive Ras signaling and not enough p53
ARF (only transcribed if signaling on “too long”)
describe ARF signaling pathway
ARF negatively regulates Mdm2 and therefore helps p53 because p53 won’t be inhibited by Mdm2
TFs for ARF
E2F when Rb hyper P
Erk 1/2 (AP1 and Ets)
how does ARF inhibit Mdm2`
binds Mdm1 and hides/sequesters Mdm2 into nucleus–> Mdm2 and ARF can’t bind p53, so p53 will accumulate, allows p53 to get P by stress sensing kinase
apoptosis vs necrosis
apoptosis: neat and ordered, usually doesn’t impact neighboring cells, everything stays contained in plasma membrane
necrosis: a lot of cells, messier (explosion), broad neg impacts –> inflammation
extrinsic apoptosis
- death receptor proteins
- no mitochondria
- death signal from diff cell
- no p53
intrinsic apoptosis
- mitochondria
- stuff inside cell signal apoptosis
- p53
explain how cancer cells get past apoptosis
apoptosis in early stages of cancer develop is important (50% cancer has mut p53) so big advantage for cancer cells to lose intrinsic apoptosis because able to survive and reproduce
initiator vs executioner caspases
initiator only cuts proteases and executioner cuts other procaspases and cuts death substrates
cell with no p53 activation
receives survival signals, has stable Bcl-2 levels, cytochrome C in mitochondria
cell with p53 activation
induce p53 to transcribe Bax
Bax
can form a pore to release cytochrome C, pro-apoptotic
Bcl2
anti-apoptotic, binds to Bax to prevent it from forming a pore