Title: LITAF, a BCL6 target gene, regulates autophagy in mature B-cell lymphomas
Authors: Bertolo, Cristina ×
Roa, Sergio
Sagardoy, Ainara
Mena-Varas, Maria
Robles, Eloy F
Martinez-Ferrandis, Jose I
Sagaert, Xavier
Tousseyn, Thomas
Orta, Alberto
Lossos, Izidore S
Amar, Salomon
Natkunam, Yasodha
Briones, Javier
Melnick, Ari
Malumbres, Raquel
Martinez-Climent, Jose A #
Issue Date: Sep-2013
Publisher: Blackwell Scientific Publications
Series Title: British Journal of Haematology vol:162 issue:5 pages:621-630
Article number: 10.1111/bjh.12440
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.
ISSN: 0007-1048
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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