DOI: 10.1126/science.1093549. Human De-Etiolated-1 Regulates c-Jun by Assembling a CUL4A Ubiquitin Ligase

Human De-Etiolated-1 Regulates c-Jun by Assembling a CUL4A Ubiquitin Ligase

10.1126/science.1093549

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

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.

Bibliography

Wertz, I. E., OâRourke, K. M., Zhang, Z., Dornan, D., Arnott, D., Deshaies, R. J., & Dixit, V. M. (2004). Human De-Etiolated-1 Regulates c-Jun by Assembling a CUL4A Ubiquitin Ligase. Science, 303(5662), 1371â1374.

Authors 7

Ingrid E. Wertz (first)
Karen M. O'Rourke (additional)
Zemin Zhang (additional)
David Dornan (additional)
David Arnott (additional)
Raymond J. Deshaies (additional)
Vishva M. Dixit (additional)

References 28 Referenced 311

10.1016/S0168-9525(98)01670-9
10.1016/0092-8674(94)90577-0
10.1126/science.1073633
10.1016/S0960-9822(02)01106-5
10.1016/S0092-8674(03)00722-0
10.1146/annurev.cellbio.19.111301.112449
10.1038/35056563
Materials and Methods are available as supporting material on Science Online.
10.1128/MCB.21.20.6738-6747.2001
10.1006/viro.2002.1773
10.1016/S0092-8674(03)00316-7
I. E. Wertz et al . data not shown.
10.1038/35013076
10.1146/annurev.cellbio.15.1.435
10.1186/1471-2121-3-30
10.1074/jbc.M212681200
10.1093/emboj/17.19.5577
10.1074/jbc.C000881200
10.1074/jbc.274.39.27674
10.1101/gad.969702
10.1016/S0962-8924(00)01834-1
H. S. Seoet al., Nature424, 995 (2003). / Nature (2003)
10.1093/emboj/20.1.118
10.1038/ncb0502-e131
10.1016/S0092-8674(94)90502-9
10.1126/science.275.5298.400
10.1038/sj.onc.1204443
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.

Dates

Type	When
Created	21 years, 6 months ago (Jan. 26, 2004, 8:23 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 10:11 p.m.)
Indexed	2 weeks, 1 day ago (Aug. 7, 2025, 4:32 p.m.)
Issued	21 years, 5 months ago (Feb. 27, 2004)
Published	21 years, 5 months ago (Feb. 27, 2004)
Published Print	21 years, 5 months ago (Feb. 27, 2004)

Funders 0

None

BibTeX

@article{Wertz_2004, title={Human De-Etiolated-1 Regulates c-Jun by Assembling a CUL4A Ubiquitin Ligase}, volume={303}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1093549}, DOI={10.1126/science.1093549}, number={5662}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Wertz, Ingrid E. and O’Rourke, Karen M. and Zhang, Zemin and Dornan, David and Arnott, David and Deshaies, Raymond J. and Dixit, Vishva M.}, year={2004}, month=feb, pages={1371–1374} }

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