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SANKAR GHOSH:
The Transcription Factor NF-κB,
An Evolutionarily Conserved Mediator of
Immune and Inflammatory Responses,
presented by Sankar Ghosh,
professor, section of Immunobiology
and Department of Molecular
Biophysics & Biochemistry,
Yale University School of Medicine.
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Inducible transcription factors play
a key role in communicating changes
in the environment
to the cell, thereby
allowing the cell to
adapt by modifying
its pattern of gene expression.
In mammalian cells, engagement
of cell surface receptors
trigger signal transduction pathways
that ultimately lead to activation
of certain transcription factors,
either through transcriptional
or post-transcriptional mechanisms.
Well-known examples of
inducible transcription factors
include steroid hormone receptors,
activating protein-1, or AP-1,
and of course, NF-κB.
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NF-κB is an
ubiquitously expressed
inducible transcription factor.
It is found in all
mammalian cells and tissues.
However, it is present
in an inactive form.
It is inactive because it is bound
to a class of inhibitory proteins
known as IκBs, and the binding
of IκB masks the nuclear
localizing signal on
NF-κB, thereby
sequestering this NF-κB/IκB
complex in the cytoplasm.
When cells are stimulated, the
activation of signal transduction
pathways ultimately lead
to the phosphorylation
and degradation of IκB,
and we'll be talking
more about in subsequent slides.
That degraded IκB then
releases the bound NF-κB,
thereby unmasking the nuclear
localizing signals on NF-κB,
which then migrates into the
nucleus and binds to NF-κB
binding sites on promoters of
gene, thereby driving NF-κB
responsive gene expression.
