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However, IRE1's kinase activity also activates the apoptosis signal-regulating kinase-1 (Ask 1)-JNK pathway via TNF receptor-associated factor 2 (TRAF2), leading to Bcl-2 phosphorylation (loss of anti-apoptotic function) and c-Jun-mediated upregulation of pro-inflammatory cytokines (e.g., TNF-, IL-6), forming a vicious cycle of ERS-inflammation-apoptosis [210]

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