Deubiquitination of RIPK3 by OTUB2 potentiates neuronal necroptosis after ischemic stroke

ABSTRACT: As a common and severe cerebrovascular disease, ischemic stroke casts a significant shadow over global health. Unfortunately, the mechanisms regulating neuronal death in the affected areas remain largely unclear. Here, we found that deletion of the deubiquitinating enzyme Otubain-2 (OTUB2) significantly alleviated ischemia-induced cerebral infarction and neurological deficits, accompanied by a reduction in neuronal loss, glial activation, and neuroinflammation. OTUB2 was predominantly expressed in neurons and its deletion decreased receptor-interacting protein kinase 3 (RIPK3)-mediated neuronal necroptosis. Moreover, OTUB2 increased RIPK3 protein abundance by inhibiting the proteasomal degradation of RIPK3. Mechanistically, OTUB2 removed K48-linked polyubiquitin chains from RIPK3 through i

SUBMITTER: Fuqi Mei 

PROVIDER: S-SCDT-10_1038-S44321-025-00206-6 | biostudies-other |

REPOSITORIES: biostudies-other