Dimerization quality control ensures neuronal development and survival

Science. 2018 Oct 12;362(6411):eaap8236. doi: 10.1126/science.aap8236.

Elijah L Mena ¹, Rachel A S Kjolby ¹, Robert A Saxton ¹, Achim Werner ², Brandon G Lew ¹, John M Boyle ¹, Richard Harland ¹, Michael Rape ³ ⁴

Affiliations

1 Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
2 National Institute of Dental and Craniofacial Research (NIDCR), NIH, Bethesda, MD 20892, USA.
3 Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. [email protected].
4 Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.

PMID: 30190310 DOI: 10.1126/science.aap8236

Abstract

Aberrant complex formation by recurrent interaction modules, such as BTB domains, leucine zippers, or coiled coils, can disrupt signal transduction, yet whether cells detect and eliminate complexes of irregular composition is unknown. By searching for regulators of the BTB family, we discovered a quality control pathway that ensures functional dimerization [dimerization quality control (DQC)]. Key to this network is the E3 ligase SCF^FBXL17, which selectively binds and ubiquitylates BTB dimers of aberrant composition to trigger their clearance by proteasomal degradation. Underscoring the physiological importance of DQC, SCF^FBXL17 is required for the differentiation, function, and survival of neural crest and neuronal cells. We conclude that metazoan organisms actively monitor BTB dimerization, and we predict that distinct E3 Ligases similarly control complex formation by other recurrent domains.

Name
Email *

	Sorry, but the email address you supplied was invalid.