Human De-Etiolated-1 Regulates c-Jun by Assembling a CUL4A Ubiquitin Ligase
Abstract
Arabidopsis thaliana De-etiolated-1 (AtDET1) is a highly conserved protein, with orthologs in vertebrate and invertebrate organisms. AtDET1 negatively regulates photomorphogenesis, but its biochemical mechanism and function in other species are unknown. We report that human DET1 (hDET1) promotes ubiquitination and degradation of the proto-oncogenic transcription factor c-Jun by assembling a multisubunit ubiquitin ligase containing DNA Damage Binding Protein-1 (DDB1), cullin 4A (CUL4A), Regulator of Cullins-1 (ROC1), and constitutively photomorphogenic-1. Ablation of any subunit by RNA interference stabilized c-Jun and increased c-Jun–activated transcription. These findings characterize a c-Jun ubiquitin ligase and define a specific function for hDET1 in mammalian cells.
Additional Information
© 2004 American Association for the Advancement of Science. 11 November 2003; Accepted 31 December 2003; Published online 22 January 2004. We thank J. Stinson, C. Grimaldi, and S. Schilbach for assistance with hCOP1 cloning; C. Reed and N. Chiang for generating hCOP1 and hDET1 antibodies; H. Maecker for fluorescence-activated cell sorting analysis assistance; J. Lee for cDNA libraries; S. Palmieri for confocal microscopy expertise, A. Waugh for bioinformatics analysis, K. Newton for editorial assistance; and G. Cope and members of the Dixit Lab for discussions. R.J.D. was supported in part by NIH grant GM065997 and is an assistant investigator of the Howard Hughes Medical Institute. I.E.W. was supported in part by a Physician Scientist Training Program fellowship from the University of California at Davis.Attached Files
Supplemental Material - Wertz.SOM.pdf
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Additional details
- Eprint ID
- 52147
- Resolver ID
- CaltechAUTHORS:20141125-123907609
- GM065997
- NIH
- Howard Hughes Medical Institute (HHMI)
- University of California, Davis
- Created
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2014-11-26Created from EPrint's datestamp field
- Updated
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2023-03-16Created from EPrint's last_modified field