TRIM2 E3 ligase substrate discovery reveals zinc regulation of TMEM106B in the endolysosomal pathway

ABSTRACT: TRIM2 is a mammalian E3 ligase with particularly high expression in Purkinje neurons, where it contributes to neuronal development and homeostasis. The understanding of ubiquitin E3 ligase function hinges on thoroughly identifying their cellular targets, but the transient nature of signaling complexes leading to ubiquitination poses a significant challenge for detailed mechanistic studies. Here, we tailored a recently developed ubiquitin-specific proximity labelling tool to identify substrates of TRIM2 in cells. We show that TRIM2 targets proteins involved in the endolysosomal pathway. Specifically, we demonstrate using biochemical and structural studies, that TRIM2 ubiquitinates TMEM106B at lysine residues located in the cytosolic N-terminal region. Substrate recognition involves a direct

SUBMITTER: Cecilia Perez-Borrajero 

PROVIDER: S-SCDT-10_1038-S44319-025-00667-3 | biostudies-other |

REPOSITORIES: biostudies-other