Nf Kb Pathway

Question 1

What types of things does NF kb respond to

Answer 1

Infection Eg via cytokines or bacterial products
Viral proteins
Dna damage
Stress

Question 2

Give an example of a sensor Eg for the cytokines

Answer 2

TLReceptors which cause signalling pathway

Question 3

Nf kb is a family of tf. Name the types

Answer 3

Rel A (p65)
Rel B
C rel

Nfkb 1 (P105) —-> p50
Nfkb 2 (P100)—-> p52

Question 4

What domain is present in all nfkb and what does it do

Answer 4

RHD

Rel homology domain - encodes the dna binding site and the dimerisation functions

Question 5

What are on p105 and p100 which allows them to act as Ikb inhibitors

Answer 5

Ankyrin repeats (lost when they convert to p50 and p52)

Question 6

How are p105 and p100 converted

Answer 6

Proteolytically processed

Question 7

What is the trans activation domain on rel A p65 called

Answer 7

TA 1 and 2

Question 8

What is the transactivation domain called on rel B and c rel

Answer 8

Rel B - TAD

C rel- sd1 and sd2

Question 9

How are ta1/2, tad and sd 1/2 different

Answer 9

They will activate and regulate differently (not homologous)

Question 10

When was nfkb first found in evolution

Answer 10

I’m multicellular organisms ie not yeast or bacteria

Question 11

Which enzymes causes ubiquitin chains to be added to proteins which are then degraded by the proteasome

Answer 11

E3 ubiquitin ligase

Question 12

What does proteasome use to degrade proteins in ubiquitination

Answer 12

Atp hydrolysis

Question 13

What is the pathway called which activates nfkb

Answer 13

Canonical pathway

Question 14

Why is nfkb rapidly activated

Answer 14

Because it is already made in the cytoplasm but stays as an inactive complex

Question 15

Which dimer is the most common of nfkb

Answer 15

P50 and rel A

Question 16

What are the 3 different types of IkB inhibitor

Answer 16

Ikb a
Ikb b
Ikb e

Question 17

Which parts of Ikb inhibitors can bind and inactivate nfkb in cytosol

Answer 17

Ankyrin repeats

Question 18

Which 2 ways does Ikb binding via ankyrin repeats inactive nfkb

Answer 18

Conformational change in it so can’t bind to dna

Hides the nuclear localisation sequence of nfkb

Question 19

How is ikb degraded

Answer 19

Phosphorylation and ubiquitination at its conserved sites

Question 20

What complex which inactivates Ikb get stimulated when w signal to switch nfkb is sensed Eg tnf a

Answer 20

Ikb kinase (IKK) complex

Question 21

What are the 3 ikk Ikb kinases

Answer 21

IKK a
IKK b
Nemo IKK y

Question 22

What 3 things make up IKK a and b

Answer 22

Kinase domain
Dna binding Eg LZ,zf,hlh
Nemo binding domain NBD

Question 23

What do IKK a and IKK b do

Answer 23

Phosphorylate and therefore cause ubiquitination of Ikb inhibitor

Question 24

How is the IKK complex made

Answer 24

1 IKK y will bind with the IKK a and ikk b nemo binding domains

Question 25

What is cc1 and cc2 on nemo IKK y

Answer 25

Coil coil domains

Question 26

Name a few things nfkb does when active

Answer 26

Inflammation via releasing cytokines Cell survival genes Cell apoptosis inducing genes Metastasis/cell adhesion inducing genes Angiogenesis Proliferation

Question 27

How does nfkb activation and production cause a feedback loop which is why nfkb is regulated via Ikb

Answer 27

Activated by cytokines and releases cytokines itself Causes constant nuclear action causing things like proliferation and inflammation

Question 28

Why are dimers like rel a p50 important

Answer 28

They bind at a specific orientation on genes to regulate them

Question 29

Once nfkb is activated via degradation of Ikb what happens in nucleus

Answer 29

Nfkb are modified Eg via phosphorylation,acetylation,de phosphorylation

Question 30

What does modification of nfkb cause

Answer 30

Either binding of co repressors or co activators Or Binding of other tf which work cooperatively or antagonistically

Question 31

What does nfkb need to get access to promoters/enhancers

Answer 31

Chromatin remodellers Eg swi2/snf2

Question 32

How are chromatin remodellers brought to allow nfkb action

Answer 32

By nfkb itself or by other proteins like HATs which attract swi/snf2 via bromodomain

Question 33

What type of co activators does rel A via modification (phosphorylation) attract to allow its access to promoters

Answer 33

Cbp/p300 Has HAT activity and recruits of TFs

Question 34

Why does nfkb get activated in viral infections

Answer 34

Viral rna activates nfkb

Question 35

Which genes are usually up regulated for antiviral/ infection response

Answer 35

Ifn b and cytokines

Question 36

Why does Sars cov cause inflammation by disrupting nfkb

Answer 36

Nfkb can’t upregualte the ifn gene which is antiviral. Only cytokines released

Question 37

Which TFs work with nfkb rel a and p50 to activate enhancer for ifn b gene

Answer 37

C jun, atf 2, irfs

Question 38

What is important in the tf recruitment on the ifn b enhancer

Answer 38

Needs to be right spacing and orientation of the c jun, atf 2 and irs and rel a/p50

Question 39

What is the binding of all tf on the ifn b called

Answer 39

Enhancesome complex

Question 40

What does the enhancesome complex do

Answer 40

Allows co activators like p300/cbp which are HATs to be attracted They allow better pic recruitment and recruit remodellers like swi2/snf2