MARIA - LECTURE 6 Flashcards
what regulates initiation of translation
of the eIF4F complex, eIF4E is the least abundant
mRNAs compete for access
how does structure of cap affect competition for eIF4F
how is eIF4F assembly controlled by mTOR
what does the mTOR pathway regulate
regulates cell size and growth
rapamycin increases lifespan
mTOR signaling pathway is the most frequently deregulated pathway in cancer cells
what kind of mRNAs are translated when eIF4F is limiting/is increased
eIF4F and cancer
associated with poorer outcome/lower survival
what does eIF2 bind
forms the ternary complex with the itRNA-met and GTP
how does the eIF2 cycle
eIF2 has three subunits, alpha subunit is phosphorylated on serine 51 by eIF2alpha kinases
eIF2 hydrolyzes GTP into GDP during translation initiation
eIF2B is in charge of bringing a new GTP to make eIF2 active again so the cycle can restart
eIF2alpha kinases sequester the complex
what are the different eIF2alpha kinases and what are their effects
by sequestering eIF2, general translation decreases and gene specific translation increases, at the same time
how does HRI (heme regulated inhibitor) work
low hemoglobin, HRI is active, blocks eIF2, low translation for globins
high hemoglobin, HRI is inactive, does not block translation
how does PKR (protein kinase R) work
what are some countermeasures that viruses have developed against PKR
how does PERK work
how does GCN2 (general control non-repressed 2) work
what is the general mechanism of GCN4 and general amino acid control (GAAC)
how is GCN4 expression controlled in non starvation conditions
there is a lot of ternary complex, a lot of eIF2, which is not phosphorylated
ribosome is recruited by ternary complex at the beginning of uORF1
at the end of uORF1, encounters stop codon, but 40S remains attached, continues scanning until uORF4, and the ribosome is released
GCN4 is not translated
how is GCN4 expression controlled in AA starvation conditions
at the end of uORF1 40S keeps scanning
low pool of TC
how does ATF4 regulation happen in stress vs non stress conditions
what is the structure of eIF2B
vanishing white matter disease and eIF2B
what does ISRIB do
ISRIB stimulates translation even through eIF2alpha is phosphorylated
how does ISRIB rescue memory during traumatic brain injury
how do we figure out how long it takes for a ribosome to translate an ORF
