title: Characterization of human constitutive photomorphogenesis protein 1, a RING finger ubiquitin ligase that interacts with Jun transcription factors and modulates their transcriptional activity.
abstract: RING finger proteins have been implicated in many fundamental cellular processes, including the control of gene expression. A key regulator of light-dependent development in Arabidopsis thaliana is the constitutive photomorphogenesis protein 1 (atCOP1), a RING finger protein that plays an essential role in translating light/dark signals into specific changes in gene transcription. atCOP1 binds the basic leucine zipper factor HY5 and suppresses its transcriptional activity through a yet undefined mechanism that results in HY5 degradation in response to darkness. Furthermore, the pleiotropic phenotype of atCOP1 mutants indicates that atCOP1 may be a central regulator of several transcriptional pathways. Here we report the cloning and characterization of the human orthologue of atCOP1. Human COP1 (huCOP1) distributes both to the cytoplasm and the nucleus of cells and shows a striking degree of sequence conservation with atCOP1, suggesting the possibility of a functional conservation as well. In co-immunoprecipitation assays huCOP1 specifically binds basic leucine zipper factors of the Jun family. As a functional consequence of this interaction, expression of huCOP1 in mammalian cells down-regulates c-Jun-dependent transcription and the expression of the AP-1 target genes, urokinase and matrix metalloproteinase 1. The RING domain of huCOP1 displays ubiquitin ligase activity in an autoubiquitination assay in vitro; however, suppression of AP-1-dependent transcription by huCOP1 occurs in the absence of changes in c-Jun protein levels, suggesting that this inhibitory effect is independent of c-Jun degradation. Our findings indicate that huCOP1 is a novel regulator of AP-1-dependent transcription sharing the important properties of Arabidopsis COP1 in the control of gene expression.
authors.affiliation: Laboratory of Leukocyte Biology, DIBIT and Universita' Vita-Salute San Raffaele, via Olgettina 58, 20132, Milan, Italy. ebianchi@pasteur.fr
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bianchi
authors.forename: Simona
authors.initials: S
authors.lastname: Denti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Catena
authors.forename: Grazisa
authors.initials: G
authors.lastname: Rossetti
authors.forename: Simona
authors.initials: S
authors.lastname: Polo
authors.forename: Sona
authors.initials: S
authors.lastname: Gasparian
authors.forename: Stella
authors.initials: S
authors.lastname: Putignano
authors.forename: Lars
authors.initials: L
authors.lastname: Rogge
authors.forename: Ruggero
authors.initials: R
authors.lastname: Pardi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D003001:Cloning, Molecular; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008025:Ligases / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; C471981:COP1 protein, human; D044767:Ubiquitin-Protein Ligases; D008025:Ligases