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Proposed mechanism of ADAM12 up-regulation by Notch. Notch activates CSL and stimulates IKK activity, leading to phosphorylation and proteasomal degradation of IκB and activation of NF-κB. NF-κB represses the transcription of miR-29, a negative regulator of ADAM12, and thus, increases ADAM12 expression. Points of action of inhibitors or activators used in this study are indicated. For details, see under “Discussion.” Act D, actinomycin D.
