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

Research output: Contribution to journalArticle

  • External authors:
  • Mariangela Sociale
  • Anna-Lena Wulf
  • Bernadette Breiden
  • Kathrin Klee
  • Melanie Thielisch
  • Franka Eckardt
  • Julia Sellin
  • Margret H Bülow
  • Sinah Löbbert
  • Nadine Weinstock
  • Joachim Schultze
  • Konrad Sandhoff
  • Reinhard Bauer

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.

Bibliographical metadata

Original languageEnglish
Pages (from-to)967-978
Number of pages12
JournalCell Reports
Volume22
Issue number4
DOIs
Publication statusPublished - 23 Jan 2018