LITAF, a BCL6 target gene, regulates autophagy in mature B-cell lymphomas

Cristina Bertolo, Sergio Roa, Ainara Sagardoy, Maria Mena-Varas, Eloy F. Robles, Jose I. Martinez-Ferrandis, Xavier Sagaert, Thomas Tousseyn, Alberto Orta, Izidore S. Lossos, Salomon Amar, Yasodha Natkunam, Javier Briones, Ari Melnick, Raquel Malumbres, Jose A. Martinez-Climent

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Abstract

We have previously reported that LITAF is silenced by promoter hypermethylation in germinal centre-derived B-cell lymphomas, but beyond these data the regulation and function of lipopolysaccharide-induced tumour necrosis factor (TNF) factor (LITAF) in B cells are unknown. Gene expression and immunohistochemical studies revealed that LITAF and BCL6 show opposite expression in tonsil B-cell subpopulations and B-cell lymphomas, suggesting that BCL6 may regulate LITAF expression. Accordingly, BCL6 silencing increased LITAF expression, and chromatin immunoprecipitation and luciferase reporter assays demonstrated a direct transcriptional repression of LITAF by BCL6. Gain- and loss-of-function experiments in different B-cell lymphoma cell lines revealed that, in contrast to its function in monocytes, LITAF does not induce lipopolysaccharide-mediated TNF secretion in B cells. However, gene expression microarrays defined a LITAF-related transcriptional signature containing genes regulating autophagy, including MAP1LC3B (LC3B). In addition, immunofluorescence analysis co-localized LITAF with autophagosomes, further suggesting a possible role in autophagy modulation. Accordingly, ectopic LITAF expression in B-cell lymphoma cells enhanced autophagy responses to starvation, which were impaired upon LITAF silencing. Our results indicate that the BCL6-mediated transcriptional repression of LITAF may inhibit autophagy in B cells during the germinal centre reaction, and suggest that the constitutive repression of autophagy responses in BCL6-driven lymphomas may contribute to lymphomagenesis. © 2013 John Wiley & Sons Ltd.
Original languageEnglish
Pages (from-to)621-630
JournalBritish Journal of Haematology
Volume162
Issue number5
DOIs
Publication statusPublished - 1 Sep 2013

Keywords

  • Autophagy
  • B cells
  • Germinal centre
  • Non-hodgkin lymphoma
  • Transcription factors

Fingerprint Dive into the research topics of 'LITAF, a BCL6 target gene, regulates autophagy in mature B-cell lymphomas'. Together they form a unique fingerprint.

Cite this