Mechanism of cullin3 E3 ubiquitin ligase dimerization

PloS One
Yin Yin Choo, Thilo Hagen

Abstract

Cullin E3 ligases are the largest family of ubiquitin ligases with diverse cellular functions. One of seven cullin proteins serves as a scaffold protein for the assembly of the multisubunit ubiquitin ligase complex. Cullin binds the RING domain protein Rbx1/Rbx2 via its C-terminus and a cullin-specific substrate adaptor protein via its N-terminus. In the Cul3 ubiquitin ligase complex, Cul3 substrate receptors contain a BTB/POZ domain. Several studies have established that Cul3-based E3 ubiquitin ligases exist in a dimeric state which is required for binding of a number of substrates and has been suggested to promote ubiquitin transfer. In two different models, Cul3 has been proposed to dimerize either via BTB/POZ domain dependent substrate receptor homodimerization or via direct interaction between two Cul3 proteins that is mediated by Nedd8 modification of one of the dimerization partners. In this study, we show that the majority of the Cul3 proteins in cells exist as dimers or multimers and that Cul3 self-association is mediated via the Cul3 N-terminus while the Cul3 C-terminus is not required. Furthermore, we show that Cul3 self-association is independent of its modification with Nedd8. Our results provide evidence for BTB s...Continue Reading

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Citations

Oct 15, 2014·Biomolecules·Cathal MahonElah Pick
Mar 5, 2016·Biochimica Et Biophysica Acta·Ghazala Mustafa, Setsuko Komatsu
Apr 29, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sarah J MeyerLars Nitschke
Jun 24, 2020·Open Biology·Sharadha Dayalan Naidu, Albena T Dinkova-Kostova
Feb 15, 2014·Journal of Biomolecular Screening·John W Cuozzo, Holly H Soutter
Mar 18, 2016·Biology of Reproduction·Maïmouna Coura KoneAmelie Bonnet-Garnier
Dec 11, 2019·The Journal of Cell Biology·Nicholas P BoyerStephanie L Gupton
Feb 23, 2021·The Plant Journal : for Cell and Molecular Biology·Shin-Yuan GuLong-Chi Wang
Jul 3, 2021·Antioxidants·Tabitha Jenkins, Jerome Gouge

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Methods Mentioned

BETA
ubiquitination
neddylation
co-immunoprecipitation
immunoprecipitation
proximity ligation
fluorescence microscopy
PCR
Infrared Imaging

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