S14-Phosphorylated RPN6 Mediates Proteasome Activation by PKA and Alleviates Proteinopathy.

ABSTRACT:

Background

A better understanding of the regulation of proteasome activities can facilitate the search for new therapeutic strategies. A cell culture study shows that PKA (cAMP-dependent protein kinase or protein kinase A) activates the 26S proteasome by pS14-Rpn6 (serine14-phosphorylated Rpn6), but this discovery and its physiological significance remain to be established in vivo.

Methods

Male and female mice with Ser14 of Rpn6 (regulatory particle non-ATPase 6) mutated to Ala (S14A [Rpn6/Psmd11^S14A]) or Asp (S14D) to respectively block or mimic pS14-Rpn6 were created and used along with cells derived from them. cAMP/PKA were manipulated pharmacologically. Ubiquitin-proteasome system functioning was evaluated with the GFPdgn (green fluorescence protein with carbo

SUBMITTER: Yang L 

PROVIDER: S-EPMC10502926 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature