lecture 6 recap Flashcards
(35 cards)
what is hypoxia
lowering of the oxygen concentrations compared to the normal levels cells are exposed to
anoxia is the
absence of oxygen completely
as a tumor grows the core becomes hypoxic, the tumor initiates
the hypoxia response
what are the 3 cellular responses to hypoxia
- restoration of oxygen
- homeostasis
- cell survival /death
HIF stands for
hypoxia inducible factor
HIF is a transcription factor, what are the two forms of HIF
HIF-alpha
HIF-1beta
3 subunits of HIF-alpha
1 alpha
2 alpha
3 alpha
HIF structure:
what mediates its DNA binding
helix-loop-helix
what domain allows HIF to activate transcription
C-terminal transactivation domain
(CTAD)
what allows HIF to respond to oxygen levels
ODD (oxygen dependent degradation) domain
which type of HIF doesnt have an ODD domain
HIF-1beta
HIF-1alpha at normal oxygen levels:
what does PHD (proline hydroxylase) do
adds OH to HIF-1a at proline residues in the ODD domain
what do hydroxylated prolines allow recruitment of
VHL (Von Hippel Lindau protein)
what is VHL
its an E3 ubiquitin ligase which stimulates ubiquitination of HIF-1a and degrades it
HIF-1a is being made continuously buts also being
degraded continuously
what is FIH
factor inhibiting HIF
what does FIH do
hydroxylases an asparagine domain in the CTAD which inhibits transcriptional activity
if oxygen levels drop the PHD and FIH cant function, why?
they require oxygen in order to induce the hydroxylation, this means HIF-1a stabilises and carrys out its functions
what does VHL bind to
hydroxylated prolines
when HIF-1a is stabilised it dimerizes with HIG-1b. this dimer is the
active transcription factor
CTAD isnt hydroxylated by FIH meaning it can bind to
p300/CBP (co activators that regulate transcription)
p53 is a
tumor suppressor and transcription factor
functions as a tetramer
p53 responds to what
DNA damage
p53 is normally inactive as its bound to its inhibitor called
mdm2
