Glycosphingolipid deficiency increases the sterol regulatory element-mediated gene transcription.
A major feedback mechanism of cholesterol in transcription of cholesterol metabolism-related genes is mediated by sterol regulatory element-binding protein (SREBP). Involvement of glycosphingolipids (GSLs) in the SREBP pathway is unknown. In this study, we examined the effects of GSL depletion on SRE-mediated gene transcription using GSL-defective cells. We found that the content of mature SREBP, the transcriptional active form, is increased in the GSL-defective cells. Transcription of SREBP target genes and cholesterol synthesis are also induced in the GSL-defective cells. These results indicate that GSL deficiency up-regulates the SREBP pathway, pointing out the regulatory role of GSL in cholesterol homeostasis.
Ishitsuka
Reiko
R
Lipid Biology Laboratory, RIKEN (Institute of Physical and Chemical Research) Advanced Science Institute, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Hirabayashi
Yoshio
Y
Kobayashi
Toshihide
T
D000818:Animals; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D006028:Glycosphingolipids / Q000172:deficiency*; D051379:Mice; D050436:Regulatory Elements, Transcriptional; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism*; D014158:Transcription, Genetic
D006028:Glycosphingolipids; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol