ZBTB18 inhibits SREBP-dependent lipid synthesis by halting CTBPs and LSD1 activity in glioblastoma

• DOI: 10.26508/lsa.202201400
• Publication Date: 2022-11-22T18:00:11Z
• Authors: Roberto Ferrarese; Annalisa Izzo; Geoffroy Andrieux; Simon Lagies; Johanna Paulina B...; Anie Priscilla Ma...; Alix Wasilenko; Daniela Osti; Stefania Faletti; Rana Schulzki; Shuai Yuan; Eva Kling; Valentino Ribecco; Dieter Henrik Hei...; Stefan Tholen; Marco Prinz; Giuliana Pelicci; Bernd Kammerer; Melanie Boerries; Maria Stella Carro
• Keywords: Fatty acid synthesis; Demethylase

Enhanced fatty acid synthesis is a hallmark of tumors, including glioblastoma. SREBF1/2 regulate the expression enzymes involved in and cholesterol synthesis. Yet, little known about precise mechanism regulating SREBP gene Here, we show that novel interaction between co-activator/co-repressor CTBP tumor suppressor ZBTB18 regulates genes. In line with our findings, metabolic assays glucose tracing analysis confirm reduction several phospholipid species upon expression. Our study identifies CTBP1/2 LSD1 as co-activators genes indicates functional activity CTBP-LSD1 complex altered by ZBTB18. binding to promoters associated reduced demethylase H3K4me2 H3K9me2 marks. Concomitantly, LSD1, CTBP, ZNF217 increased, suggesting promotes scaffolding function. results outline new epigenetic enrolled its co-factors could be targeted treat glioblastoma patients.