Primate-specific isoform of Nedd4-1 regulates substrate binding via Ser/Thr phosphorylation and 14-3-3 binding.

ABSTRACT: Nedd4 (Nedd4-1) is an E3 ubiquitin ligase involved in crucial biological processes such as growth factor receptor signaling. While canonical Nedd4-1 comprises a C2-WW₍₄₎-HECT domain architecture, alternative splicing produces non-canonical isoforms that are poorly characterized. Here we characterized Nedd4-1(NE), a primate-specific isoform of Nedd4-1 that contains a large N-terminal Extension (NE) that replaces most of the C2 domain. We show that Nedd4-1(NE) mRNA is ubiquitously expressed in human tissues and cell lines. Moreover, we found that Nedd4-1(NE) is more active than the canonical Nedd4-1 isoform, likely due to the absence of a C2 domain-mediated autoinhibitory mechanism. Additionally, we identified two Thr/Ser phosphoresidues in the NE region that act as binding sites

SUBMITTER: Kefalas G 

PROVIDER: S-EPMC10589272 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature