Dimerization quality control ensures neuronal development and survival

Abstract

A way to prevent deadly interaction Many metazoan proteins form oligomers, which is often mediated by modular domains such as BTB domains. Mena et al. now describe a quality control pathway they term dimerization quality control (DQC) (see the Perspective by Herhaus and Dikic). DQC monitors and prevents aberrant dimerization of BTB domain–containing proteins. The system relies on FBXL17, an adaptor protein that recruits an E3 ligase that specifically ubiquitylates nonfunctional BTB heterodimers, triggering their degradation. FBXL17 accesses a degradation signal at the BTB dimer interface in nonphysiological, nonfunctional complexes. The loss of DQC from Xenopus laevis embryos leads to lethal neurodevelopmental defects. Science , this issue p. eaap8236 ; see also p. 151