lecture 5 - Transcriptional responses to stress and infection (NKkB)

Question 1

the NF-kB, p53 and HIF pathways all

Answer 1

allow the cell/organism to respond to environmental threats

Question 2

NF-kB is a family of

Answer 2

5 proteins

Question 3

they can form

Answer 3

homo or hetero dimeric complexes

Question 4

rel homology domain is present in all the proteins and facilitates

Answer 4

the complexes forming

Question 5

proteins RelA RelB and c-rel form a

Answer 5

subfamiliy

Question 6

as well as the rel homology domain they also have

Answer 6

transactivation domains which allow them to work as potent activators (sometimes reporessors) of genes

Question 7

p105 and p100 are longer pre-cursor proteins which become processed into

Answer 7

p50 and p52

Question 8

ubiquitin is bound to target protein by

Answer 8

E1, E2 or E3 ligases

Question 9

NF-kB is induced by

Answer 9

inflammatory cytokines, bacterial products, viral proteins and infection, DNA damage and cell stress (there’s over 200 inducers)

Question 10

NF-kB regulates

Answer 10

the immune and inflammatory responses, stress responses, cell survival and cell death, cell adhesion and proliferation

Question 11

NF-kB dimers are held in an inactive form in the cytoplasm bound to an inhibitory protein called

Answer 11

IkB

Question 12

a ligand (eg TNFa an inflammatory cytokine) binds to a receptor at the surface and initiates

Answer 12

a signaling cascade which results in the activation of the IkB kinase complex

Question 13

this complex phosphorylates IkB which signals

Answer 13

ubiquitination of the IkB freeing NK-kB and goes to the nucleus and binds its target sequences in promotors or enhancers of the genes they regulate

Question 14

the IkB kinase complex is formed by 3 components

Answer 14

NEMO(or IKKy(gamma) , IKKa(alpha), and IKKb(beta)

Question 15

the components of the IkB family

Answer 15

have ankyrin repeats which bind the NF-kB complex and retain the complex and make it inactive

Question 16

what residue on IkB gets phorphorylated

Answer 16

serine residues

Question 17

NF-kB is released

Answer 17

rapidly after signalling

Question 18

stimulus e.g TNF or IL-1 leads to

Answer 18

phosphorylation and degradation of IkB

Question 19

phosphorylation and degradation of IkB leads to

Answer 19

translocation of NK-kB to the nucleus
modification of NK-kB subunits

Question 20

when it gets into the nucleus it can be further modified by

Answer 20

kinases, acetylases, phosphatases and more

Question 21

modifications allows them to selectively interact with other proteins eg

Answer 21

a corepressor or a coactivator which could determine whether we get expression or not

Question 22

translocation of NK-kB to the nucleus and modification of NK-kB subunits leads to

Answer 22

DNA binding and gaining access to the promoter/enhancer

Question 23

NF-kB can recruit chromatin remodellers or

Answer 23

can rely on other proteins to do this

Question 24

p300/CBP can interact and modify with the

Answer 24

RelA/p65 subunit

Question 25

the ability for RelA/p65 to interact with p300/CBP can be regulated by

Answer 25

phosphorylation of RelA as it opens up its structure and allows binding sites to emerge

Question 26

DNA binding and gaining access to the promoter/enhancer leads to

Answer 26

transactivation - interaction with the basal transcription complex and co activators