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Title: A molecular mechanism for NEMO subunit-mediated control over IκB Kinase activation in response to polyubiquitin binding

Host:  Roberto Tinoco

Abstract:  Like many protein kinases, the activation loop within a catalytic kinase domain-containing subunit of the IκB Kinase (IKK) must first be phosphorylated at specific amino acid residues before the enzyme is able to act on substrates and induce cell survival gene expression through transcription factor NF-κB.  It has been known for decades that this process requires the NEMO/IKKγ accessory subunit of IKK as well as formation of polyubiquitin chains.  We have combined information gained from structural and biophysical characterization of IKK subunit proteins with observations from in vitro and cell-based biochemical studies to arrive at a unique molecular mechanism through which IKK catalytic activation is controlled by the NEMO/IKKγ in response to its noncovalent association with linear polyubiquitin.  Our proposed mechanism predicts that this process should be amenable to be targeted selectively by small molecule compounds.  To this end, a peptide derived from NEMO has been shown to inhibit IKK activation in cells and protect mice from the NF-κB-dependent toxic effects of bacterial lipopolysaccharide.

CV:  tom_huxford_cv_123120


June 4
12:00 pm - 1:00 pm


Online – https://uci.zoom.us/j/98978941890
Irvine, California 92697

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