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

• DOI: 10.1126/science.1093549
• Publication Date: 2004-01-27T01:23:25Z
• Authors: Ingrid E. Wertz; Karen M. O'Rourke; Zemin Zhang; David Dornan; David Arnott; Raymond J. Deshaies; Vishva M. Dixit
• Keywords: Proteomics; 570; 0303 health sciences; Proto-Oncogene Proteins c-jun; Ubiquitin; Ubiquitin-Protein Ligases; Amino Acid Motifs; Molecular Sequence Data; Nuclear Proteins; Cullin Proteins; Transfection; Cell Line; DNA-Binding Proteins; 03 medical and health sciences; Genes, jun; Humans; Amino Acid Sequence; RNA, Messenger; Cloning, Molecular; RNA, Small Interfering; Carrier Proteins; Protein Binding

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.