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

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. (2004) Human De-Etiolated-1 Regulates c-Jun by Assembling a CUL4A Ubiquitin Ligase. Science, 303 (5662). pp. 1371-1374. ISSN 0036-8075. doi:10.1126/science.1093549.

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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.

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Deshaies, Raymond J.0000-0002-3671-9354
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.
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Howard Hughes Medical Institute (HHMI)UNSPECIFIED
University of California, DavisUNSPECIFIED
Issue or Number:5662
Record Number:CaltechAUTHORS:20141125-123907609
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Official Citation:Wertz, I. E., O'Rourke, 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), 1371-1374. doi: 10.1126/science.1093549
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52147
Deposited On:26 Nov 2014 15:52
Last Modified:10 Nov 2021 19:21

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