GV5: Inducible Transcription Factors Flashcards
what drives the gene transcription process
driven by availability/activation of transcription factors, accessibility of DNA, chromatin structure (DNA & histone proteins), requires coactivator proteins to unwind DNA
what is histone acetylation
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
what is heterochromatin
densely packed nucleosomes, condensed
not actively transcribed, deacetylated histones
what is euchromatin
extended ‘beads on a string’ appearance
being actively transcribed, acetylated histones
what does NFkB stand for
nuclear factor of Kappa (light chain) in B cells
what is the role of NFkB
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
what activates NFkB
bacterial/viral infection
stress/UV/ROI
cytokines, IL-1, TNFalpha
what is the process between NFkB and inflammation
free radicals IL-1 -> NFkB -> COX -> inflammatory prostaglandins
what is AP-1
activator protein -1
what does AP-1 do
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
what role does AP-1 have
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
what happens in proliferation
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
what is the Go stage of the cell cycle
resting phase
what is the G1 stage of cell cycle
Gap! - cell prepares for DNA synthesis
ensure it is large enough, has sufficient nutrients and all external growth stimuli are present
what is the S-phase stage of cell cycle
DNA replicated/synthesised
what is the G2 phase of the cell cycle
Gap2 - cells prepares for division
what is the M-phase of the cell cycle
mitosis, spindle formation and cell division
what are the two families of proteins involved in molecular basis of cell cycle control
cyclins (transcription dependent)
cyclin-dependent kinases (activation dependent)
phosphorylation by CDKs key in controlling cell cycle
which cell cycle stage utilises cyclinD/CDK4/6
G1
which cell cycle stage utilises cyclinE/CDK2
end of G1
which cell cycle stage utilises cyclinA/CDK2
S
which cell cycle utilises cyclinB/CDK1
G2
what cyclins and CDKs are involved in cell cycle
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
what are the two groups of CDK inhibitors
INK4 which inhibits CDK4/6
CIP/Kip which inhibits all CDKs
what are CDK inhibitors used for
transcriptionally regulated, bind cyclin/cdk complexes to prevent activation, inhibits cell cycle leading to growth suppression, overall balance between cyclin/CDKs is important
