title: The tumour antigen PRAME is a subunit of a Cul2 ubiquitin ligase and associates with active NFY promoters.
abstract: The human tumour antigen PRAME (preferentially expressed antigen of melanoma) is frequently overexpressed in tumours. High PRAME levels correlate with poor clinical outcome of several cancers, but the mechanisms by which PRAME could be involved in tumourigenesis remain largely elusive. We applied protein-complex purification strategies and identified PRAME as a substrate recognition subunit of a Cullin2-based E3 ubiquitin ligase. PRAME can be recruited to DNA in vitro, and genome-wide chromatin immunoprecipitation experiments revealed that PRAME is specifically enriched at transcriptionally active promoters that are also bound by NFY and at enhancers. Our results are consistent with a role for the PRAME ubiquitin ligase complex in NFY-mediated transcriptional regulation.
authors.affiliation: Department of Molecular Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
authors.forename: Adalberto
authors.initials: A
authors.lastname: Costessi
authors.forename: Nawel
authors.initials: N
authors.lastname: Mahrour
authors.forename: Esther
authors.initials: E
authors.lastname: Tijchon
authors.forename: Rieka
authors.initials: R
authors.lastname: Stunnenberg
authors.forename: Marieke A
authors.initials: MA
authors.lastname: Stoel
authors.forename: Pascal W
authors.initials: PW
authors.lastname: Jansen
authors.forename: Dotan
authors.initials: D
authors.lastname: Sela
authors.forename: Skylar
authors.initials: S
authors.lastname: Martin-Brown
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.forename: Joan W
authors.initials: JW
authors.lastname: Conaway
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Conaway
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D044842:Cullin Proteins / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D023081:CCAAT-Binding Factor; C105153:CUL2 protein, human; D044842:Cullin Proteins; C404944:PRAME protein, human; D021122:Protein Subunits; C402244:nuclear factor Y; D044767:Ubiquitin-Protein Ligases