Lecture 11 - Protein homeostasis 1 Flashcards
protein homeostasis is the maintaining of the correct amount of what where?
functional proteins inside and out of the cell
which molecule is an example of protein regulation by negative feedback?
p53
which molecule binds to p53 and targets it for degradation by the proteasome?
Mdm2
cellular stress leads to an …… of p53, leading to an increase in …… therefore
increase, Mdm2
what are the 6 stages in the life cycle of a protein?
synthesis, folding, transport, modifications, function, degradation
give an example of a signalling pathway which leads to changes in translation when dysregulated in protein synthesis?
mTOR
name the 3 types of protein folding
chaperone independent, Hsp-70 assisted, Hsp-70 and chaperonin complex assisted
in chaperone independednt folding, where does the protein fold as it is synthesised?
on the ribosome
in Hsp-70 assisted protein folding, Hsp-70 binds to what as they are synthesised to help them fold?
newly forming polypeptides
Chaperones prevent misfolded or
incompletely assembled proteins
from exiting which cellular structure?
the ER
the unfolded protein response (UPR) is caused by an increase of what? what does the UPR lead to?
misfolded proteins in the ER, apoptosis
name the 4 reversible covalent protein modifications
phosphorylation, glycosylation, acetylation, ubiquitination
undesired protein modifications come from which 2 reactive species?
ROS, RNS
name the 2 major classes of protein damage
conformational and covalent
name some causes of conformational changes to proteins
heating, free radicals, chemicals, pH change
name some causes of covalent damage to proteins
oxidation, isomerisation, carbonylation, formation of isoaspartate
give an example of a molecular chaperone
Hsp90
after stress what happens to the regulation of molecular chaperones? what do they do to proteins?
they are upregulated, can fold proteins, prevent protein aggregation, target proteins for degradation
which 2 heat shock chaperone proteins are involved in the stress response?
Hsp70 and 90
which 2 heat shock chaperone proteins are involved in preventing aggregation?
Hsp40 and small heat shock proteins
which 3 heat shock chaperone proteins are involved in protein folding?
Hsp60, 70, 90
which heat shock protein chaperone is anti apoptotic?
Hsp60
which 2 heat shock chaperone proteins are involved in protein degradation?
Hsp70, 90
which heat shock protein chaperone interacts with steroid receptors?
Hsp90
in the prevention of protein aggregation, which exposed part of the misfolded proteins do chaperons bind to, to stop proteins sticking ?
hydrophobic region
which gene regulates the txn of heat shock genes?
HSF1
which gene is normally present as inactive monomers but forms homotrimers in stressed cells?
HSF1
in HSF1, trimers are activated and translocate to the nucleus where they bind to what?
HSE
name the 4 types of signalling proteins which Hsp70 and 90 interact with?
nuclear hormone receptors, protein kinases, cell cycle regulators, cell death regulators
which Hsp regulates glucocorticoid receptor signalling?
Hsp90
does the HSF1 transcriptional response and therefore heat shock response decline with age?
yes
what is the name of the hypothesis in which an increase in misfolded proteins and a decrease in available chaperones causes defects in signal transduction and immune function?
chaperone overload hypothesis
