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Life Science

PD Dr. Reinhard Bauer, Entwicklungsgenetik und Molekulare Physiologie, Life & Medical Sciences-Institut (LIMES), Universität Bonn, Bonn, Germany

DKFZ, H2.02.073, Main Building, Second Floor, Im Neuenheimer Feld 280

German Cancer Research Center

Maintenance of metabolic homeostasis requires adaption of gene regulation to the cellular energy state via transcriptional regulators. We identified a role of ceramide synthase (CerS) Schlank as a transcriptional regulator. Schlank binds promoter regions of lipases lipase3 and magro via its homeodomain. Mutations in the homeodomain consequently lead to loss of DNA binding and deregulated gene expression, and loss of transcriptional adjustment to changing lipid levels. This mechanism is conserved in mammalian CerS2 and emphasizes the importance of the CerS protein besides the ceramide Synthesis as there is 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. Deregulation of these processes may lead ultimatively to the formation of cancer like it is observed in aged CerS2-deficient mice.

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