HIF Pathway Flashcards
In which situations does the hif pathway get activated
Hypoxic environments Eg altitudes
Hif is hypoxia indictable factor
What can happen to cells in hyperoxia
Oxidative stress
Why is hypoxia relevant to cancer and what does hif and nfkb do
Cancer tumours become hypoxic because no vessels
Hif and nfkb promote angiogenesis
Name ways cells can react to hypoxia to restore survival or induce death
Dna replication blocked
Translation blocked to conserve energy
Transcriptional changes
Chromatin change
What makes up a hif dimer
Hif 1a and hif 1b
How is hif 1a different to hif 2a
Hif 1a is expressed in all tissues
How is hif 3a different
Lacks c terminal activation domain CTAD and nuclear localisation signal
Is hif 1a regulated or hif 1b
Hif 1a
Which dna binding domain does Hif have
Basic HLH helix loop helix
Which domain is important for HIF1a/2a degradation in presence of oxygen
ODD oxygen dependant domain
N terminal domain
What does hif 1b not have
ODD/NTAD
NLS
CTAD
What gets hydroxylated on the ODD of hif1a
Proline
What gets hydroxylsted on the CTAD of Hif 1a which inhibits the transactivated domain via FIH
Asparagine
During high oxygen levels what keeps hif being degraded and how
Phd
They hydroxylate the proline on the ODD
What does hydroxylation of proline on ODD of Hif 1a do
Attracts protein called VHL which causes ubiquitination of hif1a
Then degraded by proteasome
When in hypoxic conditions what happens to hif 1a
Phd can’t hydroxylase proline on the odd which means VHL isn’t attracted and ubiquitination can’t occur so hif1a stays active
When is FIH active to inactivate the CTAD via asparagine hydroxylstion
When o2 is present
Which part of the hif1a hif1b heterodimer binds to coactivators like p300/cbp HAT to regulate gene expression
CTAD on hif1a
What types of genes does hif target in hypoxia
Erythropoietin to increase RBC Carry of oxygen
Other than hypoxic gene responses what other genes does hif dimer regulate with coactivator p300/cbp
Metabolism
Cell death
Cell growth
