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Science 303 (5662): 1371-1374

Copyright © 2004 by the American Association for the Advancement of Science

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

Ingrid E. Wertz,1,4 Karen M. O'Rourke,1 Zemin Zhang,2 David Dornan,1 David Arnott,3 Raymond J. Deshaies,5 Vishva M. Dixit1*

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.

1 Department of Molecular Oncology, Genentech, Inc., South San Francisco, CA 94080, USA.
2 Department of Bioinformatics, Genentech, Inc., South San Francisco, CA 94080, USA.
3 Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA 94080, USA.
4 Department of Biological Chemistry, School of Medicine, University of California, Davis, CA 95616, USA.
5 Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

* To whom correspondence should be addressed. E-mail: dixit{at}gene.com

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