PRAME Is a Golgi-Targeted Protein That Associates with the Elongin BC Complex and Is Upregulated by Interferon-Gamma and Bacterial PAMPs

Wadelin, Frances R.; Fulton, Joel; Collins, Hilary M.; Tertipis, Nikolaos; Bottley, Andrew; Spriggs, Keith A.; Falcone, Franco H.; Heery, David M.

Abstract

Preferentially expressed antigen in melanoma (PRAME) has been described as a cancer-testis antigen and is associated with leukaemias and solid tumours. Here we show that PRAME gene transcription in leukaemic cell lines is rapidly induced by exposure of cells to bacterial PAMPs (pathogen associated molecular patterns) in combination with type 2 interferon (IFN?). Treatment of HL60 cells with lipopolysaccharide or peptidoglycan in combination with IFN? resulted in a rapid and transient induction of PRAME transcription, and increased association of PRAME transcripts with polysomes. Moreover, treatment with PAMPs/IFN? also modulated the subcellular localisation of PRAME proteins in HL60 and U937 cells, resulting in targeting of cytoplasmic PRAME to the Golgi. Affinity purification studies revealed that PRAME associates with Elongin B and Elongin C, components of Cullin E3 ubiquitin ligase complexes. This occurs via direct interaction of PRAME with Elongin C, and PRAME colocalises with Elongins in the Golgi after PAMP/IFN? treatment. PRAME was also found to co-immunoprecipitate core histones, consistent with its partial localisation to the nucleus, and was found to bind directly to histone H3 in vitro. Thus, PRAME is upregulated by signalling pathways that are activated in response to infection/inflammation, and its product may have dual functions as a histone-binding protein, and in directing ubiquitylation of target proteins for processing in the Golgi.

Citation

Wadelin, F. R., Fulton, J., Collins, H. M., Tertipis, N., Bottley, A., Spriggs, K. A., …Heery, D. M. (2013). PRAME Is a Golgi-Targeted Protein That Associates with the Elongin BC Complex and Is Upregulated by Interferon-Gamma and Bacterial PAMPs. PLoS ONE, 8(2), Article e58052. https://doi.org/10.1371/journal.pone.0058052

• Journal Article Type: Article
• Acceptance Date: Jan 30, 2013
• Online Publication Date: Feb 27, 2013
• Publication Date: Feb 27, 2013
• Deposit Date: Aug 3, 2020
• Publicly Available Date: Sep 25, 2020
• Journal: PLoS ONE
• Electronic ISSN: 1932-6203
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 2
• Article Number: e58052
• DOI: https://doi.org/10.1371/journal.pone.0058052
• Keywords: General Biochemistry, Genetics and Molecular Biology; General Agricultural and Biological Sciences; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/4808423
• Publisher URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058052