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CMB2001 > L5-6: transcriptional responses to stress and infection > Flashcards

L5-6: transcriptional responses to stress and infection Flashcards

1
Q

environmental challenges to cells

A

DNA damage
infection
hypoxia
physical stress

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2
Q

effector outcomes from environmental challenges

A

gene expression
repair
programmed death
immune response

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3
Q

NF-kB

A

nuclear factor of kappa immunoglobulin light chain in B cells

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4
Q

NF-kB function

A

response to external threat via expression regulation of target genes for survival/ recovery/ death induction

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5
Q

RHD

A

rel homology domain
mediates DNA binding and dimerisation functions of NF-kB

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6
Q

origin of p50/ p52

A

proteolytically processed from P105 / p100 precursor

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7
Q

p100 precursor

A

inducible

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8
Q

p105 precursor

A

constitutive

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9
Q

2 sub families of NF-kB

A

Rel family
p105/p100

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10
Q

relA

A

p65

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11
Q

Rel family

A

C-terminal txn activation domain > txn activators

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12
Q

p105/ p100

A

longer precursor proteins > protolytically cleaved to form active DNA - binding components
ankyrin repeats in C termini > IkB-like inhibitors

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13
Q

NF-kB evolution

A

coincided w need for innate immunity
initially found in eukaryotes as single gene

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14
Q

E3 ubiquitin ligase

A

76 amino acid
facilitates ubiquitin chain attachment to a target protein at Lysine
can form chains w self

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15
Q

protein degradation

A

ATP-dependent process w 3 enzymes

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16
Q

E3 ubiquitin ligase complex for proteasome recognition

A

26 Ub molecules sufficient for 26s proteasome recognition

17
Q

Ubiquitin proteasome pathway

A

Ub recognised by 26S proteasome complex
Ub attached at Lys to protein
degradation
Ub removed and linearized/ injected into proteasome core
digested to peptides
either broken down by peptidases > amino acids or used for antigen presentation

18
Q

NF-KB induction

A

inflam cytokines
bacterial products
viral proteins/ infection
DNA damage
cell stress

19
Q

what does NF-kB regulate

A

immune/ inflam response
stress response
cell survival and death
cell adhesion
proliferation

20
Q

where is NFkB retained?

A

cytoplasm in inactive form > bound to inhibitor protein IkB

21
Q

what happens when NFkB is stimulated

A

IkB phosphorylated and ubiquitin attached
26S proteasome degradation
free NF-kB translocates to nucleus

22
Q

IKK

A

IkB kinase

23
Q

IKK complex

A

3 sub-units:
IKK alpha
IKK beta (catalytic)
IKK delta/ NEMO (NF-kB essential modifier > regulatory)

24
Q

inhibitors of IkB kinase

A

IkB alpha
IkB beta b
IkB beta e
Bcl3

25
Q

characteristics of IKK inhibitors

A

Ankyrin repeat motifs in C termini
PEST domain rich (proline/ glutamate/ serine/ threonine)

26
Q

alternative pathway for NF-kB activation

A

phosphorylates p100 cursor protein
activates / partially processes to p52

27
Q

canonical vs non-canonical pathway for NF-kB activation

A

canonical activates p50RelA heterodimer
non-canonical activates p52 relB heterodimer

28
Q

NF-kB responses

A

inflammation
proliferation
survival
tumor promotion/ metastasis
angiogenesis
cell death/ anti proliferative effects

29
Q

NF-kB/ IKK gene knockout effects

A

apoptosis/ immunity/ inflammation
cells abberantly nuclear (diseased)
constitutive activity

30
Q

NF-kB binding site

A

imperfect palindrome\
> orientates NF-kB specifically

31
Q

what happens to NF-kB once it enters the nucleus?

A

kinases/ acetylases modify
moderated txn response
cooperates / antagonizes other txn factors

32
Q

promoter enhancers

A

regulate genes
complex array of binding sites for variety of txn factors

33
Q

differential chromatin states at NFkB dependent genes

A

promoter enhancers can be inaccessible in cell, can recruit remodellers
HAT/Swi/Snf CAT-dependent remodellers

34
Q

beta interferon

A

NFkB regulated gene
produced in response to viral infection (and alpha)
bind CSR for signalling cascade for activation of 50 anti-viral genes

35
Q

multimerisation of beta interferon enhancer

A

act as viral inducible promoter
varying basal activity, responding to other inducers
HMGI/HMGAI assisted

36
Q

interaction interface of enhanceosome complex

A

allows high affin recruitment of txn coactivators (p300/CBP)

37
Q

combination lock of NFkB

A

p50/ RelA complex at beta ifn enhancer

38
Q

basal transcription machinery

A

NFkB recruits to induce transcription

39
Q
A

CMB2001 (4 decks)

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