Repression of sphingosine kinase (SK)-interacting protein (SKIP) in acute myeloid leukemia diminishes SK activity and its re-expression restores SK function.

ABSTRACT: Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrati

SUBMITTER: Ghazaly EA 

PROVIDER: S-EPMC7170527 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature