RT Journal Article
SR Electronic
T1 ZBTB18 inhibits SREBP-dependent lipid synthesis by halting CTBPs and LSD1 activity in glioblastoma
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201400
DO 10.26508/lsa.202201400
VO 6
IS 1
A1 Roberto Ferrarese
A1 Annalisa Izzo
A1 Geoffroy Andrieux
A1 Simon Lagies
A1 Johanna Paulina Bartmuss
A1 Anie Priscilla Masilamani
A1 Alix Wasilenko
A1 Daniela Osti
A1 Stefania Faletti
A1 Rana Schulzki
A1 Shuai Yuan
A1 Eva Kling
A1 Valentino Ribecco
A1 Dieter Henrik Heiland
A1 Stefan Tholen
A1 Marco Prinz
A1 Giuliana Pelicci
A1 Bernd Kammerer
A1 Melanie Boerries
A1 Maria Stella Carro
YR 2023
UL https://www.life-science-alliance.org/content/6/1/e202201400.abstract
AB Enhanced fatty acid synthesis is a hallmark of tumors, including glioblastoma. SREBF1/2 regulate the expression of enzymes involved in fatty acid and cholesterol synthesis. Yet, little is known about the precise mechanism regulating SREBP gene expression in glioblastoma. Here, we show that a novel interaction between the co-activator/co-repressor CTBP and the tumor suppressor ZBTB18 regulates the expression of SREBP genes. In line with our findings, metabolic assays and glucose tracing analysis confirm the reduction in several phospholipid species upon ZBTB18 expression. Our study identifies CTBP1/2 and LSD1 as co-activators of SREBP genes and indicates that the functional activity of the CTBP-LSD1 complex is altered by ZBTB18. ZBTB18 binding to the SREBP gene promoters is associated with reduced LSD1 demethylase activity of H3K4me2 and H3K9me2 marks. Concomitantly, the interaction between LSD1, CTBP, and ZNF217 is increased, suggesting that ZBTB18 promotes LSD1 scaffolding function. Our results outline a new epigenetic mechanism enrolled by ZBTB18 and its co-factors to regulate fatty acid synthesis that could be targeted to treat glioblastoma patients.