Leture 6 - Transcriptional responses to stress 2 - p53 + HIF pathways Flashcards
define hypoxia in terms of lowering O2 levels
hypoxia = lowering of the O2 concentrations compared to sea level +/- 20.9%
What does HIF stand for?
hypoxia inducible factor
what are the 2 subunits which make up HIF, a heterodimeric transcription factor?
HIF alpha, HIF beta
true or false, HIF- 1 alpha is ubiquitously expressed in ALL tissues?
true
which terminus domain does HIF-alpha 3 lack?
does it function as a promoter or inhibitor for HIF-alpha 1+2?
C-terminus transactivation domain
inhibitor
which domain of the HIF-alpha subunits responds to changes in oxygen levels?
the ODD domain
In the ODD domain on HIF-alpha subunits, what are the proline residues modified by when responding to changes in oxygen?
hydroxyl groups/hydroxylation
what is the name for the group of enzymes which regulate HIF, requiring oxygen to function?
proline hydroxylases
name some targets (pathways) that HIF aims to control
oxygen supply, cell growth, cell death, cell metabolism, transcription
true or false, p53 is a tumour promoter and a transcription factor?
false. p53 is a tumour SUPPRESSOR as well as a transcription factor
name the 4 domains of p53
transactivation domain
proline rich domain
nuclear localisation sequence
tetramerisation domain
p53 is known as the ‘guardian of the genome’, maintaining cellular and genetic stability. hence it controls the ……. of the cell cycle and also apoptosis.
arrest of cell cycle
in a normal cell, p53 is inactivated by its negative regulator called what?
how does it inactivate p53
Mdm2
via ubiquitination
inactivation of Mdm2 by which tumour suppressor results in increased levels of transcriptionally active p53?
p14 ARF
in cancer cells, is p53 highly mutated to become inactive, meaning that the cell cycle is not arrested = uncontrollable cell growth?
yes p53 is highly mutated
