Journal Article Review Ppublish 1 citation
PubMed: 39477759 DOI: 10.1016/j.molmed.2024.10.006
Promoting proteostasis by cAMP/PKA and cGMP/PKG.
Trends Mol Med 31(3):224-239
Authors: Md Salim Ahammed, Xuejun Wang
Affiliations
- Division of Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine, Vermillion, SD 57069, USA.
- Division of Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine, Vermillion, SD 57069, USA.
Abstract
Proteasome functional insufficiency (PFI) is implicated in neurodegeneration and heart failure, where aberrant protein aggregation is common and impairs the ubiquitin (Ub)-proteasome system (UPS), exacerbating increased proteotoxic stress (IPTS) and creating a vicious circle. Breaking this circle represents a key to treating these diseases. Protein kinase (PK)-A and PKG can activate the proteasome and promote proteasomal degradation of misfolded proteins. PKA does so by phosphorylating Ser14-RPN6/PSMD11, but how PKG activates the proteasome remains unknown. Emerging evidence supports a strategy to treat diseases with IPTS by augmenting cAMP/PKA and cGMP/PKG. Conceivably, targeted activation of PKA and PKG at proteasome nanodomains would minimize the undesired effects from their actions on other targets. In this review, we discuss PKA and PKG regulation of proteostasis via the UPS.
MeSH
Heart Failure, Proteasome Endopeptidase Complex, Neurodegenerative Diseases