Proteasomal regulation of ASK family kinases dictates cell fate under hyperosmotic stress.

ABSTRACT: The proteasome has an essential role in proteostasis maintenance and is critical for cell survival under proteotoxic conditions, including hyperosmotic stress. However, how proteasome activity is linked to cell survival/death under hyperosmotic stress is unclear. We previously reported that apoptosis signal-regulating kinase 3 (ASK3) contributes to cell survival through its inactivation under hyperosmotic stress. The 19S regulatory particle subunits of the proteasome were enriched in the ASK3 inactivator candidates identified through our genome-wide siRNA screening. In this study, we demonstrated that the proteasome regulates ASK3 inactivation through its proteolytic activity. Intriguingly, the proteasome inactivates ASK3 via degradation of not ASK3 per se but another ASK family member, AS

SUBMITTER: Zhou X 

PROVIDER: S-EPMC12446641 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature