Ceramide Synthase doing double duty as transcriptional regulator

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We believe that these results significantly broaden our understanding of how an organism adapts to metabolic changes in health and disease. Our concept will challenge the dogma that most regulatory aspects of CerSs are exclusively based on the enzyme activity and the ceramide produced and shift the focus on the CerS protein. The identification of a mechanism for the CerS as a regulator coordinating genomic response to altered metabolic conditions, represents an important step in unravelling the molecular network underlying lipid-based metabolic disorders. This mechanism could have clinical implications for pathologies associated with ceramide- or metabolic disorders such as neurodegeneration (e.g. Zellweger Syndrome), obesity and insulin resistance leading to diabetes. Since the function of the CerSs homeodomain as transcriptional regulator identified in this study is new, it will open the possibility of alternative therapeutic approaches. We believe that this is a major discovery and is of fundamental interest to cell biology, in particular on lipid research, signal transduction and metabolism and metabolic related diseases in general.

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