Evidence for Functional Regulation of the KLHL3/WNK Pathway by O-GlcNAcylation.

ABSTRACT: The 42-member Kelch-like (KLHL) protein family are adaptors for ubiquitin E3 ligase complexes, governing the stability of a wide range of substrates. KLHL proteins are critical for maintaining proteostasis in a variety of tissues and are mutated in human diseases, including cancer, neurodegeneration, and familial hyperkalemic hypertension. However, the regulation of KLHL proteins remains incompletely understood. Previously, we reported that two KLHL family members, KEAP1 and gigaxonin, are regulated by O-linked β-N-acetylglucosamine (O-GlcNAc), an intracellular form of glycosylation. Interestingly, some ubiquitination targets of KEAP1 and gigaxonin are themselves also O-GlcNAcylated, suggesting that multi-level control by this posttranslational modification may influence many KLHL p

SUBMITTER: Hu J 

PROVIDER: S-EPMC11888436 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature