Ceramide Synthase Schlank Is a Transcriptional Regulator Adapting Gene Expression to Energy Requirements

Sociale, Mariangela; Wulf, Anna Lena; Breiden, Bernadette; Klee, Kathrin; Thielisch, Melanie; Eckardt, Franka; Sellin, Julia; Bülow, Margret H.; Löbbert, Sinah; Weinstock, Nadine; Voelzmann, André; Schultze, Joachim; Sandhoff, Konrad; Bauer, Reinhard

Abstract

Maintenance of metabolic homeostasis requires adaption of gene regulation to the cellular energy state via transcriptional regulators. Here, we identify a role of ceramide synthase (CerS) Schlank, a multiple transmembrane protein containing a catalytic lag1p motif and a homeodomain, which is poorly studied in CerSs, as a transcriptional regulator. ChIP experiments show that it binds promoter regions of lipases lipase3 and magro via its homeodomain. Mutation of nuclear localization site 2 (NLS2) within the homeodomain leads to loss of DNA binding and deregulated gene expression, and NLS2 mutants can no longer adjust the transcriptional response to changing lipid levels. This mechanism is conserved in mammalian CerS2 and emphasizes the importance of the CerS protein rather than ceramide synthesis. This study demonstrates a double role of CerS Schlank as an enzyme and a transcriptional regulator, sensing lipid levels and transducing the information to the level of gene expression. Sociale et al. report that the ceramide synthase Schlank, a multiple transmembrane protein containing a catalytic lag1p motif and a homeodomain, can act as a transcriptional regulator.

Citation

Sociale, M., Wulf, A. L., Breiden, B., Klee, K., Thielisch, M., Eckardt, F., Sellin, J., Bülow, M. H., Löbbert, S., Weinstock, N., Voelzmann, A., Schultze, J., Sandhoff, K., & Bauer, R. (2018). Ceramide Synthase Schlank Is a Transcriptional Regulator Adapting Gene Expression to Energy Requirements. Cell reports, 22(4), 967-978. https://doi.org/10.1016/j.celrep.2017.12.090

• Journal Article Type: Article
• Acceptance Date: Dec 25, 2017
• Online Publication Date: Jan 28, 2018
• Publication Date: Jan 23, 2018
• Deposit Date: Feb 8, 2024
• Publicly Available Date: Feb 22, 2024
• Journal: Cell Reports
• Print ISSN: 2211-1247
• Electronic ISSN: 2211-1247
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 22
• Issue: 4
• Pages: 967-978
• DOI: https://doi.org/10.1016/j.celrep.2017.12.090
• Keywords: Ceramide synthase; Homeodomain; Transcription factors; Energy homeostasis; Lipid metabolism; Genomic engineering; Peroxisome; Lipid sensing
• Public URL: https://hull-repository.worktribe.com/output/4371797