The ubiquitin ligase Nedd4-2 promotes localization of DNMBP/Tuba to P-bodies under hyperosmotic stress.

ABSTRACT: The ubiquitin ligase Nedd4-2/NEDD4L, comprised of C2-WW(x4)-HECT domains, is known to regulate several ion transporters and channels. We recently showed that elevated intracellular [Na⁺] and osmolarity enhances Nedd4-2 enzymatic activity. To globally identify its interactome and substrates in cells under hyperosmotic stress, we performed a BioID screen using miniTurbo with Nedd4-2 as a bait under hyperosmotic (vs. isosmotic) conditions. One of the top hits identified that preferentially binds Nedd4-2 under hyperosmolarity was Dynamin Binding Protein (DNMBP)/Tuba, a known GEF for Cdc42. We then showed that DNMBP is a substrate for Nedd4-2, and that active Nedd4-2 targets DNMBP to P-body condensates under hyperosmotic stress. Moreover, DNMBP itself promotes P-body formation under

SUBMITTER: Liu Z 

PROVIDER: S-EPMC12569825 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature