A Protein Quality Control Pathway Regulated by Linear Ubiquitination

ABSTRACT: Neurodegenerative diseases are characterized by the accumulation of misfolded proteins in the brain. Insights into protein quality control mechanisms to prevent neuronal dysfunction and cell death are crucial in developing causal therapies. Here we report that various diseases-associated protein aggregates are modified by the linear ubiquitin chain assembly complex (LUBAC). HOIP, the catalytic component of LUBAC is recruited to misfolded Huntingtin in a p97/VCP-dependent manner, resulting in the assembly of linear polyubiquitin. As a consequence, the interactive surface of misfolded Huntingtin species is shielded from unwanted interactions, for example with the low complexity sequence domain-containing transcription factor Sp1, and proteasomal degradation of misfolded Huntingtin is facilit

SUBMITTER: Prof. Konstanze, F Winklhofer 

PROVIDER: S-SCDT-EMBOJ-2018-100730 | biostudies-other |

REPOSITORIES: biostudies-other