Aryl hydrocarbon receptor interacting protein maintains germinal center B cells through suppression of BCL6 degradation

Research output: Contribution to journalArticle

Authors

  • Dijue Sun
  • Urszula Stopka-Farooqui
  • Sayka Barry
  • Ezra Askoy
  • Gregory Parsonage
  • Anna Vossenkamper
  • Melanie Capasso
  • Xinyu Wan
  • Sherine Norris
  • Andrew Clear
  • John Gribben
  • Thomas T. MacDonald
  • Marta Korbonits
  • Oliver Haworth

Colleges, School and Institutes

External organisations

  • William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
  • Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.

Abstract

B cell lymphoma-6 (BCL6) is highly expressed in germinal center B cells, but how its expression is maintained is still not completely clear. Aryl hydrocarbon receptor interacting protein (AIP) is a co-chaperone of heat shock protein 90. Deletion of Aip in B cells decreased BCL6 expression, reducing germinal center B cells and diminishing adaptive immune responses. AIP was required for optimal AKT signaling in response to B cell receptor stimulation, and AIP protected BCL6 from ubiquitin-mediated proteasomal degradation by the E3-ubiquitin ligase FBXO11 by binding to the deubiquitinase UCHL1, thus helping to maintain the expression of BCL6. AIP was highly expressed in primary diffuse large B cell lymphomas compared to healthy tissue and other tumors. Our findings describe AIP as a positive regulator of BCL6 expression with implications for the pathobiology of diffuse large B cell lymphoma. BCL6 overexpression contributes to the pathobiology of diffuse large B cell lymphoma (DLBCL). Sun et al. find that the co-chaperone aryl hydrocarbon receptor interacting protein (AIP), whose high expression is associated with reduced survival of DLBCL patients, helps maintain BCL6 expression by facilitating the removal of ubiquitin from BCL6.

Details

Original languageEnglish
Article numbere4
Pages (from-to)1464-1471
JournalCell Reports
Volume27
Issue number5
Early online date30 Apr 2019
Publication statusE-pub ahead of print - 30 Apr 2019