Aryl Hydrocarbon Receptor Interacting Protein Maintains Germinal Center B Cells through Suppression of BCL6 Degradation

Cell Rep. 2019 Apr 30;27(5):1461-1471.e4. doi: 10.1016/j.celrep.2019.04.014.

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.

Keywords: AIP; BCL6; FBXO11; UCHL1; lymphoma; ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • B-Lymphocytes / immunology*
  • F-Box Proteins / metabolism
  • Female
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / immunology*
  • Male
  • Mice
  • Middle Aged
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Binding
  • Protein-Arginine N-Methyltransferases / metabolism
  • Proteolysis
  • Proto-Oncogene Proteins c-bcl-6 / metabolism*
  • Ubiquitin Thiolesterase / metabolism
  • Ubiquitination

Substances

  • BCL6 protein, human
  • F-Box Proteins
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • UCHL1 protein, human
  • aryl hydrocarbon receptor-interacting protein
  • FBXO11 protein, human
  • Protein-Arginine N-Methyltransferases
  • Ubiquitin Thiolesterase
  • Proteasome Endopeptidase Complex