The human EKC/KEOPS complex is recruited to cullin2 ubiquitin ligases by the human tumour antigen PRAME

Adalberto Costessi, Nawel Mahrour, Vikram Sharma, Rieka Stunnenberg, Marieke A. Stoel, Esther Tijchon, Joan W. Conaway, Ronald C. Conaway, Hendrik G. Stunnenberg

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

The human tumour antigen PRAME (preferentially expressed antigen in melanoma) is frequently overexpressed during oncogenesis, and high PRAME levels are associated with poor clinical outcome in a variety of cancers. However, the molecular pathways in which PRAME is implicated are not well understood. We recently characterized PRAME as a BC-box subunit of a Cullin2-based E3 ubiquitin ligase. In this study, we mined the PRAME interactome to a deeper level and identified specific interactions with OSGEP and LAGE3, which are human orthologues of the ancient EKC/KEOPS complex. By characterizing biochemically the human EKC complex and its interactions with PRAME, we show that PRAME recruits a Cul2 ubiquitin ligase to EKC. Moreover, EKC subunits associate with PRAME target sites on chromatin. Our data reveal a novel link between the oncoprotein PRAME and the conserved EKC complex and support a role for both complexes in the same pathways.

Original languageEnglish (US)
Article numbere42822
JournalPloS one
Volume7
Issue number8
DOIs
StatePublished - Aug 13 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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