20mM aspirin

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1994
IkB concentrations in the salicylate cell
extracts were the same as in control whereas IkB
was reduced in activated cells without salicylate
20mM aspirin
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CREB
NFkB NFkB
Not seeing the same inhibition profile as other
antiinflammatory agents.
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Other antiinflammatory drugs inhibit
prostaglandin synthesis but they do not alter IKK
activity
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Inhibition of IKK activity is unique to ASA and
Sal Only IKKbeta inhibited
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Effective ASA 1-5mM
Other pathways
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IKK SS-gtEE mutations (constitutively active)
Not upstream of IKK
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Recombinant IKK beta - same trend as in vivo
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in vivo in vitro
80uM 30-50uM
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Suggest not covalently bound
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preincubation
Inhibition of kinase activity dept. of aspirin
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How does this relate to cancer?
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Many Faces of Ubiquitin - Deubiquitinating Enzymes
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Familial Cylindromatosis (benign tumors) Usually
on forehead and scalp Dominantly inherited due
to loss of the tumor suppressor CYLD
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Used siRNA to knockdown expression of CYLD
PMA (phorbol ester) stimulates NFkB via IkBalpha
degradation When KD CYLD - increased
proliferation
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16hours later
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