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Strickland, B.A.* ; Babl, A.* ; Wolff, L.* ; Singh, P. ; Friano, M.E.* ; Greulich, F.* ; Uhlenhaut, N.H.

C-terminal binding protein 2 interacts with JUNB to control macrophage inflammation.

Life Sci. All. 8:16 (2025)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Although acute inflammatory responses are critical for survival, chronic inflammation is a leading cause of disease and mortality worldwide. Nevertheless, our mechanistic understanding of pathogenesis is still limited and precise treatment options are lacking. Here, we investigate the role of the transcriptional co-repressors C-terminal binding protein (CTBP) 1 and 2 in murine and human macrophage activation using loss-of-function models to show that CTBP2 but not CTBP1 controls inflammatory gene expression. We find that CTBP2 occupies cis-regulatory elements of inflammatory genes together with the transcription factors NF-κB and AP-1 and forms a co-repressor complex. Rescue of Ctbp1/2 double knockout cells with WT, oligomeric CTBP2 attenuates inflammatory responses, whereas a monomeric mutant does not. Differential profiling of CTBP2's WT and monomeric interactome confirms oligomer-specific interactions with multiple repressors. Conversely, monomers retain the ability to interact with AP-1 and RNA polymerase II, boosting gene expression. Our findings point to an important function for CTBP2 in fine-tuning inflammatory gene expression, potentially unveiling novel therapeutic targets for the treatment of inflammatory diseases.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Proinflammatory Cytokines; Ctbp; Lsd1; Activation; Mechanisms; Inhibition; Repressor; Package; Hdac1
ISSN (print) / ISBN 2575-1077
e-ISSN 2575-1077
Journal Life Science Alliance
Quellenangaben Volume: 8, Issue: 8, Pages: , Article Number: 16 Supplement: ,
Publisher EMBO Press
Publishing Place Heidelberg
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Endocrinology (IDE)
Grants International Helmholtz-Edinburgh Research School for Epigenetics
TUM Global Incentive Funds
DFG
German Research Foundation DFG
Novo Nordisk Foundation (NNF)
Next Generation Sequencing Competence Network (NGS-CN)
DFG Research Infrastructure Program