NF-kappaB, and not MYCN, regulates MHC class I and endoplasmic reticulum aminopeptidases in human neuroblastoma cells

Cancer Research
Matteo ForloniDoriana Fruci

Abstract

Neuroblastoma (NB) is the most common solid extracranial cancer of childhood. Amplification and overexpression of the MYCN oncogene characterize the most aggressive forms and are believed to severely downregulate MHC class I molecules by transcriptional inhibition of the p50 NF-kappaB subunit. In this study, we found that in human NB cell lines, high MYCN expression is not responsible for low MHC class I expression because neither transfection-mediated overexpression nor small interfering RNA suppression of MYCN affects MHC class I and p50 levels. Furthermore, we identified NF-kappaB as the immediate upstream regulator of MHC class I because the p65 NF-kappaB subunit binds MHC class I promoter in chromatin immunoprecipitation experiments, and MHC class I expression is enhanced by p65 transfection and reduced by (a) the chemical NF-kappaB inhibitor sulfasalazine, (b) a dominant-negative IKBalpha gene, and (c) p65 silencing. Moreover, we showed that the endoplasmic reticulum aminopeptidases ERAP1 and ERAP2, which generate MHC class I binding peptides, are regulated by NF-kappaB, contain functional NF-kappaB-binding elements in their promoters, and mimic MHC class I molecules in the expression pattern. Consistent with these findin...Continue Reading

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Citations

Jun 9, 2009·American Journal of Respiratory Cell and Molecular Biology·Sara BusaccaGiovanni Gaudino
Jan 26, 2013·Journal of Neuroinflammation·Avanita S PrabowoEleonora Aronica
Sep 4, 2012·International Journal of Molecular Sciences·Loredana CifaldiDoriana Fruci
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Aug 23, 2020·International Journal of Molecular Sciences·Ombretta MelaiuDoriana Fruci
Aug 29, 2020·Signal Transduction and Targeted Therapy·Min LuoLiwu Fu
Oct 10, 2018·Cancer Research·Dinoop Ravindran MenonMayumi Fujita
Feb 12, 2021·International Journal of Molecular Sciences·Silvia D'AmicoDoriana Fruci
May 2, 2021·Cancer Reports·Anders Valind, David Gisselsson
Aug 7, 2021·Journal for Immunotherapy of Cancer·Ahmet HaziniLen Seymour
Sep 30, 2021·Scientific Reports·Alexandre Chagas SantanaEberval Gadelha Figueiredo
Nov 9, 2021·Frontiers in Immunology·Karolina PiekarskaIzabela Nowak

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