Phosphorylation of IkB-a Inhibits Its Cleavage by Caspase CPP32 in Vitro*
نویسندگان
چکیده
IkB proteins function as direct regulators of Rel/ NF-kB transcription complexes. We show that the celldeath protease CPP32 (caspase-3) in vitro specifically cleaved chicken and human IkB-a at a conserved Asp-Ser sequence. This cleavage site appears to be identical to the site at which chicken IkB-a is cleaved in vivo in temperature-sensitive v-Rel-transformed chicken spleen cells undergoing apoptosis. Other caspases, namely interleukin-1bconverting enzyme (caspase-1) and Ich-1 (caspase-2), did not cleave IkB-a. CPP32 also cleaved mammalian IkB-b in vitro at the analogous Asp-Ser sequence. Cleavage of IkB-a by CPP32 was blocked by serine phosphorylation of IkB-a. Cleavage of IkB-a by a CPP32like protease could generate a constitutive inhibitor of Rel transcription complexes. This report provides evidence for a direct biochemical interaction between the NF-kB signaling pathway and a celldeath protease signaling pathway.
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