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TNF induces tyrosine phosphorylation of Mule via Syk, which then leads to the dissociation of the inhibitory ARF from Mule. Mule becomes activated and catalyzes the K48-linked polyubiquitination of Miz1, promoting its degradation. Degradation of Miz1 relieves its suppression on JNK, allowing JNK to be activated and leading to cell death.
