1. Academic Validation
  2. The tumour antigen PRAME is a subunit of a Cul2 ubiquitin ligase and associates with active NFY promoters

The tumour antigen PRAME is a subunit of a Cul2 ubiquitin ligase and associates with active NFY promoters

  • EMBO J. 2011 Aug 5;30(18):3786-98. doi: 10.1038/emboj.2011.262.
Adalberto Costessi 1 Nawel Mahrour Esther Tijchon Rieka Stunnenberg Marieke A Stoel Pascal W Jansen Dotan Sela Skylar Martin-Brown Michael P Washburn Laurence Florens Joan W Conaway Ronald C Conaway Hendrik G Stunnenberg
Affiliations

Affiliation

  • 1 Department of Molecular Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
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.

Figures