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PRAME is a golgi-targeted protein that associates with the Elongin BC complex and is upregulated by interferon-gamma

Frances R Wadelin1, Joel Fulton, Hilary M Collins

  • 1School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, United Kingdom.

Plos One
|March 6, 2013
PubMed

Insights

Preferentially expressed antigen in melanoma (PRAME) gene transcription is rapidly induced by pathogen-associated molecular patterns (PAMPs) and interferon-gamma (IFNγ). PRAME protein is targeted to the Golgi and interacts with histone-binding and ubiquitylation complexes.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • Preferentially expressed antigen in melanoma (PRAME) is a cancer-testis antigen linked to various cancers, including leukaemias and solid tumours.
  • The regulatory mechanisms and functional roles of PRAME, particularly in response to immune stimuli, remain incompletely understood.

Purpose of the Study:

  • To investigate the regulation of PRAME gene transcription by immune signaling pathways.
  • To elucidate the functional interactions and subcellular localization of PRAME protein in response to specific stimuli.

Main Methods:

  • Leukaemic cell lines (HL60, U937) were treated with bacterial pathogen-associated molecular patterns (PAMPs) and type 2 interferon (IFNγ).
  • PRAME gene transcription and polysome association were analyzed. Subcellular localization of PRAME protein was studied using immunofluorescence.
  • Affinity purification and co-immunoprecipitation were employed to identify PRAME-interacting proteins, including Elongins and histones.

Main Results:

  • PAMPs/IFNγ treatment rapidly and transiently induced PRAME transcription and increased polysome association in leukaemic cells.
  • PRAME protein was targeted to the Golgi apparatus following PAMPs/IFNγ stimulation.
  • PRAME was found to associate with Elongin B/C of Cullin E3 ubiquitin ligase complexes and directly bind to histone H3.

Conclusions:

  • PRAME is upregulated by signaling pathways activated during infection and inflammation.
  • PRAME may possess dual functions: binding histones and potentially directing ubiquitylation of target proteins for processing in the Golgi.

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