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Cylindromatosis mediates neuronal cell death in vitro and in vivo.

ABSTRACT: The tumor-suppressor cylindromatosis (CYLD) is a deubiquitinating enzyme and key regulator of cell proliferation and inflammation. A genome-wide siRNA screen linked CYLD to receptor interacting protein-1 (RIP1) kinase-mediated necroptosis; however, the exact mechanisms of CYLD-mediated cell death remain unknown. Therefore, we investigated the precise role of CYLD in models of neuronal cell death in vitro and evaluated whether CYLD deletion affects brain injury in vivo. In vitro, downregulation of CYLD increased RIP1 ubiquitination, prevented RIP1/RIP3 complex formation, and protected neuronal cells from oxidative death. Similar protective effects were achieved by siRNA silencing of RIP1 or RIP3 or by pharmacological inhibition of RIP1 with necrostatin-1. In vivo, CYLD knockout mice were protected from trauma-induced brain damage compared to wild-type littermate controls. These findings unravel the mechanisms of CYLD-mediated cell death signaling in damaged neurons in vitro and suggest a cell death-mediating role of CYLD in vivo.

SUBMITTER: Ganjam GK

PROVIDER: S-EPMC6113218 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Cylindromatosis mediates neuronal cell death in vitro and in vivo.

Ganjam Goutham K GK Terpolilli Nicole Angela NA Diemert Sebastian S Eisenbach Ina I Hoffmann Lena L Reuther Christina C Herden Christiane C Roth Joachim J Plesnila Nikolaus N Culmsee Carsten C

Cell death and differentiation 20180119 8

The tumor-suppressor cylindromatosis (CYLD) is a deubiquitinating enzyme and key regulator of cell proliferation and inflammation. A genome-wide siRNA screen linked CYLD to receptor interacting protein-1 (RIP1) kinase-mediated necroptosis; however, the exact mechanisms of CYLD-mediated cell death remain unknown. Therefore, we investigated the precise role of CYLD in models of neuronal cell death in vitro and evaluated whether CYLD deletion affects brain injury in vivo. In vitro, downregulation o ...[more]

PMID: 29352268

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Cylindromatosis mediates neuronal cell death in vitro and in vivo.

Publications

Cylindromatosis mediates neuronal cell death in vitro and in vivo.

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