GV5: Inducible Transcription Factors Flashcards

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1
Q

what drives the gene transcription process

A

driven by availability/activation of transcription factors, accessibility of DNA, chromatin structure (DNA & histone proteins), requires coactivator proteins to unwind DNA

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2
Q

what is histone acetylation

A

histone proteins have many basic amino acids with positive charge
enables interaction with negative phosphate backbone of DNA
acetylation blocks ability to bind DNA by masking positive charge
relaxes interaction of DNA with nucleosome

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3
Q

what is heterochromatin

A

densely packed nucleosomes, condensed

not actively transcribed, deacetylated histones

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4
Q

what is euchromatin

A

extended ‘beads on a string’ appearance

being actively transcribed, acetylated histones

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5
Q

what does NFkB stand for

A

nuclear factor of Kappa (light chain) in B cells

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6
Q

what is the role of NFkB

A

ubiquitous transcription factor, generally associated with the activation of inflammatory genes
all contain conserved sequence known as Rel domain which regulates dimerization and nuclear localisation
inhibited by IkB which binds across the Rel domain

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7
Q

what activates NFkB

A

bacterial/viral infection
stress/UV/ROI
cytokines, IL-1, TNFalpha

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8
Q

what is the process between NFkB and inflammation

A

free radicals IL-1 -> NFkB -> COX -> inflammatory prostaglandins

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9
Q

what is AP-1

A

activator protein -1

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10
Q

what does AP-1 do

A

regulates immediate early response genes, regulates a number of cellular functions including cell growth, compromises a dimer of the Fos and Jun families, requires transcription of Fos family member and phosphorylation of Jun family member

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11
Q

what role does AP-1 have

A

regulates many genes involved in cell growth and differentiation
role in bone development and implicated in inflammation
may have a role in long term memory

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12
Q

what happens in proliferation

A

cells are signalled to proliferate through the binding of growth factors to receptors
activation of intracellular signalling pathways leads to gene transcription
gene transcription results in the expression of proteins required to drive the cell through the cell cycle
process is tightly controlled to prevent aberrant proliferation

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13
Q

what is the Go stage of the cell cycle

A

resting phase

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14
Q

what is the G1 stage of cell cycle

A

Gap! - cell prepares for DNA synthesis

ensure it is large enough, has sufficient nutrients and all external growth stimuli are present

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15
Q

what is the S-phase stage of cell cycle

A

DNA replicated/synthesised

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16
Q

what is the G2 phase of the cell cycle

A

Gap2 - cells prepares for division

17
Q

what is the M-phase of the cell cycle

A

mitosis, spindle formation and cell division

18
Q

what are the two families of proteins involved in molecular basis of cell cycle control

A

cyclins (transcription dependent)
cyclin-dependent kinases (activation dependent)
phosphorylation by CDKs key in controlling cell cycle

19
Q

which cell cycle stage utilises cyclinD/CDK4/6

A

G1

20
Q

which cell cycle stage utilises cyclinE/CDK2

A

end of G1

21
Q

which cell cycle stage utilises cyclinA/CDK2

A

S

22
Q

which cell cycle utilises cyclinB/CDK1

A

G2

23
Q

what cyclins and CDKs are involved in cell cycle

A

growth factor stimulation, transcription of c-fos, activation of c-jun, transcription of cyclin D, cyclin D1 levels rise, cyclin D/CDK4 complexes, CDK4 phosphorylates pRb, pRb releases E2F, E2F active - required for transcription of cyclin E

24
Q

what are the two groups of CDK inhibitors

A

INK4 which inhibits CDK4/6

CIP/Kip which inhibits all CDKs

25
Q

what are CDK inhibitors used for

A

transcriptionally regulated, bind cyclin/cdk complexes to prevent activation, inhibits cell cycle leading to growth suppression, overall balance between cyclin/CDKs is important