Principal Investigator: Tom Huxford, Ph.D
Goal: The major focus of the laboratory is in understanding regulation in the transcription factor NF-kappaB signal transduction pathway.
Project: The relationship between NF-kappaB and its Inhibitor IkappaB-zeta studied via site specific chemoenzymatic biojunjugation of IkappaB-zeta and GFP.
Involvement: September 2014 - Present
NF-κB is an inducible transcription factor that controls the expression of numerous stress response genes. The prototypical NF-κB protein functions as a complex composed of two subunits known as p50 and p65. In resting cells NF-κB exists in an inactive state within the cell cytoplasm through its non-covalent association with a separate inhibitory protein known as IκB. In response to diverse environmental stimuli, the inhibitory IκB protein becomes phosphorylated, marking it for degradation via the ubiquitin-dependent 26 S Proteasome-mediated system. Free of its inhibitor, NF-κB rapidly migrates into the nucleus where it binds to specific DNA sequences located within promoter regions of target genes leading to their increased expression. Elevated expression of most target genes relies upon the presence of the NF-κB p65 subunit. However, significant amounts of p50:p50 homodimer can be detected in the nucleus of resting cells. Upon induction, this nuclear p50 homodimer is a target for binding by a class of nuclear IkB protein known as IκBζ. Eventually, we hope to use these assays to identify small molecules that specifically inhibit complex formation of p50 and IκBζ.
Goal: The major focus of the laboratory is in understanding regulation in the transcription factor NF-kappaB signal transduction pathway.
Project: The relationship between NF-kappaB and its Inhibitor IkappaB-zeta studied via site specific chemoenzymatic biojunjugation of IkappaB-zeta and GFP.
Involvement: September 2014 - Present
NF-κB is an inducible transcription factor that controls the expression of numerous stress response genes. The prototypical NF-κB protein functions as a complex composed of two subunits known as p50 and p65. In resting cells NF-κB exists in an inactive state within the cell cytoplasm through its non-covalent association with a separate inhibitory protein known as IκB. In response to diverse environmental stimuli, the inhibitory IκB protein becomes phosphorylated, marking it for degradation via the ubiquitin-dependent 26 S Proteasome-mediated system. Free of its inhibitor, NF-κB rapidly migrates into the nucleus where it binds to specific DNA sequences located within promoter regions of target genes leading to their increased expression. Elevated expression of most target genes relies upon the presence of the NF-κB p65 subunit. However, significant amounts of p50:p50 homodimer can be detected in the nucleus of resting cells. Upon induction, this nuclear p50 homodimer is a target for binding by a class of nuclear IkB protein known as IκBζ. Eventually, we hope to use these assays to identify small molecules that specifically inhibit complex formation of p50 and IκBζ.