Nf Kb Pathway Flashcards
What types of things does NF kb respond to
Infection Eg via cytokines or bacterial products
Viral proteins
Dna damage
Stress
Give an example of a sensor Eg for the cytokines
TLReceptors which cause signalling pathway
Nf kb is a family of tf. Name the types
Rel A (p65)
Rel B
C rel
Nfkb 1 (P105) —-> p50 Nfkb 2 (P100)—-> p52
What domain is present in all nfkb and what does it do
RHD
Rel homology domain - encodes the dna binding site and the dimerisation functions
What are on p105 and p100 which allows them to act as Ikb inhibitors
Ankyrin repeats (lost when they convert to p50 and p52)
How are p105 and p100 converted
Proteolytically processed
What is the trans activation domain on rel A p65 called
TA 1 and 2
What is the transactivation domain called on rel B and c rel
Rel B - TAD
C rel- sd1 and sd2
How are ta1/2, tad and sd 1/2 different
They will activate and regulate differently (not homologous)
When was nfkb first found in evolution
I’m multicellular organisms ie not yeast or bacteria
Which enzymes causes ubiquitin chains to be added to proteins which are then degraded by the proteasome
E3 ubiquitin ligase
What does proteasome use to degrade proteins in ubiquitination
Atp hydrolysis
What is the pathway called which activates nfkb
Canonical pathway
Why is nfkb rapidly activated
Because it is already made in the cytoplasm but stays as an inactive complex
Which dimer is the most common of nfkb
P50 and rel A
What are the 3 different types of IkB inhibitor
Ikb a
Ikb b
Ikb e
Which parts of Ikb inhibitors can bind and inactivate nfkb in cytosol
Ankyrin repeats
Which 2 ways does Ikb binding via ankyrin repeats inactive nfkb
Conformational change in it so can’t bind to dna
Hides the nuclear localisation sequence of nfkb
How is ikb degraded
Phosphorylation and ubiquitination at its conserved sites
What complex which inactivates Ikb get stimulated when w signal to switch nfkb is sensed Eg tnf a
Ikb kinase (IKK) complex
What are the 3 ikk Ikb kinases
IKK a
IKK b
Nemo IKK y
What 3 things make up IKK a and b
Kinase domain
Dna binding Eg LZ,zf,hlh
Nemo binding domain NBD
What do IKK a and IKK b do
Phosphorylate and therefore cause ubiquitination of Ikb inhibitor
How is the IKK complex made
1 IKK y will bind with the IKK a and ikk b nemo binding domains
What is cc1 and cc2 on nemo IKK y
Coil coil domains
Name a few things nfkb does when active
Inflammation via releasing cytokines
Cell survival genes
Cell apoptosis inducing genes
Metastasis/cell adhesion inducing genes
Angiogenesis
Proliferation
How does nfkb activation and production cause a feedback loop which is why nfkb is regulated via Ikb
Activated by cytokines and releases cytokines itself
Causes constant nuclear action causing things like proliferation and inflammation
Why are dimers like rel a p50 important
They bind at a specific orientation on genes to regulate them
Once nfkb is activated via degradation of Ikb what happens in nucleus
Nfkb are modified Eg via phosphorylation,acetylation,de phosphorylation
What does modification of nfkb cause
Either binding of co repressors or co activators
Or
Binding of other tf which work cooperatively or antagonistically
What does nfkb need to get access to promoters/enhancers
Chromatin remodellers Eg swi2/snf2
How are chromatin remodellers brought to allow nfkb action
By nfkb itself or by other proteins like HATs which attract swi/snf2 via bromodomain
What type of co activators does rel A via modification (phosphorylation) attract to allow its access to promoters
Cbp/p300
Has HAT activity and recruits of TFs
Why does nfkb get activated in viral infections
Viral rna activates nfkb
Which genes are usually up regulated for antiviral/ infection response
Ifn b and cytokines
Why does Sars cov cause inflammation by disrupting nfkb
Nfkb can’t upregualte the ifn gene which is antiviral.
Only cytokines released
Which TFs work with nfkb rel a and p50 to activate enhancer for ifn b gene
C jun, atf 2, irfs
What is important in the tf recruitment on the ifn b enhancer
Needs to be right spacing and orientation of the c jun, atf 2 and irs and rel a/p50
What is the binding of all tf on the ifn b called
Enhancesome complex
What does the enhancesome complex do
Allows co activators like p300/cbp which are HATs to be attracted
They allow better pic recruitment and recruit remodellers like swi2/snf2
