lecture 6 recap

Question 1

what is hypoxia

Answer 1

lowering of the oxygen concentrations compared to the normal levels cells are exposed to

Question 2

anoxia is the

Answer 2

absence of oxygen completely

Question 3

as a tumor grows the core becomes hypoxic, the tumor initiates

Answer 3

the hypoxia response

Question 4

what are the 3 cellular responses to hypoxia

Answer 4

1. restoration of oxygen
2. homeostasis
3. cell survival /death

Question 5

HIF stands for

Answer 5

hypoxia inducible factor

Question 6

HIF is a transcription factor, what are the two forms of HIF

Answer 6

HIF-alpha
HIF-1beta

Question 7

3 subunits of HIF-alpha

Answer 7

1 alpha
2 alpha
3 alpha

Question 8

HIF structure:
what mediates its DNA binding

Answer 8

helix-loop-helix

Question 9

what domain allows HIF to activate transcription

Answer 9

C-terminal transactivation domain
(CTAD)

Question 10

what allows HIF to respond to oxygen levels

Answer 10

ODD (oxygen dependent degradation) domain

Question 11

which type of HIF doesnt have an ODD domain

Answer 11

HIF-1beta

Question 12

HIF-1alpha at normal oxygen levels:
what does PHD (proline hydroxylase) do

Answer 12

adds OH to HIF-1a at proline residues in the ODD domain

Question 13

what do hydroxylated prolines allow recruitment of

Answer 13

VHL (Von Hippel Lindau protein)

Question 14

what is VHL

Answer 14

its an E3 ubiquitin ligase which stimulates ubiquitination of HIF-1a and degrades it

Question 15

HIF-1a is being made continuously buts also being

Answer 15

degraded continuously

Question 16

what is FIH

Answer 16

factor inhibiting HIF

Question 17

what does FIH do

Answer 17

hydroxylases an asparagine domain in the CTAD which inhibits transcriptional activity

Question 18

if oxygen levels drop the PHD and FIH cant function, why?

Answer 18

they require oxygen in order to induce the hydroxylation, this means HIF-1a stabilises and carrys out its functions

Question 19

what does VHL bind to

Answer 19

hydroxylated prolines

Question 20

when HIF-1a is stabilised it dimerizes with HIG-1b. this dimer is the

Answer 20

active transcription factor

Question 21

CTAD isnt hydroxylated by FIH meaning it can bind to

Answer 21

p300/CBP (co activators that regulate transcription)

Question 22

p53 is a

Answer 22

tumor suppressor and transcription factor
functions as a tetramer

Question 23

p53 responds to what

Answer 23

DNA damage

Question 24

p53 is normally inactive as its bound to its inhibitor called

Answer 24

mdm2

Question 25

if the cell receives a DNA damage stimulus mdm2 becomes

Answer 25

inactivated and p53 active

Question 26

primary respopnse of p53 is

Answer 26

cell cycle arrest

Question 27

what is cell cycle arrest

Answer 27

cell stops proliferating allows a chance for the DNA repair

Question 28

is DNA damage is too severe p53 induces

Answer 28

apoptosis eliminating the damaged cell

Question 29

mdm2 is also a

Answer 29

E3 ubiquitin ligase

Question 30

p53 and mdm2 get phosphorylated by ATM kinases what does this disrupt

Answer 30

interactions between p53 and mdm2

Question 31

p53 also regulates the activity of what

Answer 31

mdm2 forming a negative feedback loop that limits the extent of p53 activation

Question 32

p14ARF is induced by increased by what

Answer 32

increased cellular proliferation

Question 33

what does p14ARF bind to

Answer 33

mdm2 and blocks it from binding to p53 and increases levels of p53

Question 34

most types of cancer are caused by

Answer 34

inactivation of p53

Question 35

inactivation of p53 can occur through

Answer 35

mutation of ATM kinases