Model of endosomal stress (IMAGE)

Tokyo Metropolitan Institute of Medical Science

Model of endosomal stress

Caption

Endosomal stress, the aberrant accumulation of K63 ubiquitin chains on dysfunctional endosomes, activates the TAB2/3–TAK1–NF-kB and p62–Keap1–Nrf2 pathways, resulting in the expression of immune and stress response genes such as CCL5 and SOD2. TAB2/3 and p62 associate with excess K63 ubiquitin chains accumulated on endosomes. TAB2/3 induces NF-kB through activation of TAK1 while p62 induces Nrf2 through sequestration of Keap1, an Nrf2-targeting E3 ligase.

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TMiMS

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