The UDP-glucose ceramide glycosyltransferase (UGCG) and the link to multidrug resistance protein 1 (MDR1)

BMC Cancer

Peter Mattjus¹  Gerd Geisslinger²  Marthe-Susanna Wegner²  Lisa Gruber²  Sabine Grösch² 

[1] Biochemistry, Faculty of Science and Engineering, Åbo Akademi University;pharmazentrum frankfurt/ ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University;

关键词: UDP-glucose ceramide glycosyltransferase;    UGCG;    Glycosphingolipids;    MDR1;    P-gp;    Multidrug resistance;   

DOI  :  10.1186/s12885-018-4084-4

来源: DOAJ

【 摘 要 】

Abstract The UDP-glucose ceramide glycosyltransferase (UGCG) is a key enzyme in the sphingolipid metabolism by generating glucosylceramide (GlcCer), the precursor for all glycosphingolipids (GSL), which are essential for proper cell function. Interestingly, the UGCG is also overexpressed in several cancer types and correlates with multidrug resistance protein 1 (MDR1) gene expression. This membrane protein is responsible for efflux of toxic substances and protects cancer cells from cell damage through chemotherapeutic agents. Studies showed a connection between UGCG and MDR1 overexpression and multidrug resistance development, but the precise underlying mechanisms are unknown. Here, we give an overview about the UGCG and its connection to MDR1 in multidrug resistant cells. Furthermore, we focus on UGCG transcriptional regulation, the impact of UGCG on cellular signaling pathways and the effect of UGCG and MDR1 on the lipid composition of membranes and how this could influence multidrug resistance development. To our knowledge, this is the first review presenting an overview about UGCG with focus on the relationship to MDR1 in the process of multidrug resistance development.

【 授权许可】

Unknown