Lecture 5 - Transcriptional responses to stress - NFkB pathway

Question 1

name 4 environmental / physiological stresses which trigger the NFkB pathway

Answer 1

hypoxia, DNA damage, infection, physical stress

Question 2

which domain of NFKB encodes the DNA binding and dimerisation functions?

Answer 2

Rel homology domain (RHD)

Question 3

name 3 things which NFKB regulates to do with cells in the body

Answer 3

cell adhesion
cell survival and death
cell proliferation

Question 4

how many NFKB families are there in mammalian cells?

Answer 4

5

Question 5

in order to bind to DNA, NFKB must form what?

Answer 5

dimers

Question 6

true or false, NFKB can be induced by inflammatory cytokines?

Answer 6

true

Question 7

true or false, NFKB can be induced by viruses and bacteria?

Answer 7

true

Question 8

true or false, NFKB can regulate angiogenesis?

Answer 8

true

Question 9

NFKB is an inactive cytoplasmic complex. Give an example of a ligand which can activate it.

Does the ligand activate it directly or indirectly?

Answer 9

TNF alpha

indirectly

Question 10

how do ligands, for example TNF alpha, activate the inactive cytoplasmic NFKB complex? ( 5 step process)

Answer 10

ligands activate IKK kinase

IKK kinase phosphorylates IKB

IKB is ubiquitinated as IKK marks it for ubiquitination

IKB gets degraded = activates NFKB

NFKB translated to nucleus

Question 11

what does IKK phosphorylate?

Answer 11

IKB

Question 12

which 2 catalytic subunits and which regulatory subunit make up the IkB kinase (IKK complex)?

Answer 12

IKK gamma (NEMO) is regulatory

IKK alpha and
IKK beta are both catalytic

Question 13

which ligands activate NFkB indirectly through the canonical (classical pathway)?

Answer 13

TNF alpha
IL-1
LPS

Question 14

which ligands activate NFkB indirectly through the non-canonical (alternative pathway)?

Answer 14

CD40
LPS
LMP1

Question 15

after NFkB has been translocated to the nucleus, which type of remodellers can it recruit?

what does NFkB also then interact with in order to activate a transcriptional response?

Answer 15

chromatin remodellers

basal transcription complex to initiate transcription

Question 16

NFKB complexes are held in an 1)……… form in the cytoplasm, bound to the inhibitory protein: 2)………

When this is 3)……… by the IKK complex, it becomes 4)……… and degraded, freeing NFkB to 5) ……… to the nucleus

Answer 16

1 - inactive
2 - IkB
3 - phosphorylated
4 - ubiquitinated
5 - translocated