title: 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.
authors.affiliation: Department of Molecular Oncology, Genentech, Inc., South San Francisco, CA 94080, USA.
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Wertz
authors.forename: Karen M
authors.initials: KM
authors.lastname: O'Rourke
authors.forename: Zemin
authors.initials: Z
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Dornan
authors.forename: David
authors.initials: D
authors.lastname: Arnott
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Deshaies
authors.forename: Vishva M
authors.initials: VM
authors.lastname: Dixit
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D016758:Genes, jun; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D040901:Proteomics; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*
chemical_list: C114234:CUL4A protein, human; D002352:Carrier Proteins; D044842:Cullin Proteins; C091435:DDB1 protein, human; C482641:DET1 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016755:Proto-Oncogene Proteins c-jun; C479529:RBX1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D025801:Ubiquitin; C471981:COP1 protein, human; D044767:Ubiquitin-Protein Ligases