COP9 signalosome controls the degradation of cytosolic misfolded proteins and protects against cardiac proteotoxicity.

ABSTRACT:

Rationale

Impaired degradation of misfolded proteins is associated with a large subset of heart diseases. Misfolded proteins are degraded primarily by the ubiquitin-proteasome system, but the ubiquitin ligases responsible for the degradation remain largely unidentified. The cullin deneddylation activity of the COP9 signalosome (CSN) requires all 8 CSN subunits (CSN1 through CSN8) and regulates cullin-RING ligases, thereby controlling ubiquitination of a large number of proteins; however, neither CSN nor cullin-RING ligases is known to regulate the degradation of cytosolic misfolded proteins.

Objective

We sought to investigate the role of CSN8/CSN in misfolded protein degradation and cardiac proteinopathy.

Methods and results

Cardiac CSN8 knockout causes mouse prematur

SUBMITTER: Su H 

PROVIDER: S-EPMC4636927 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature