It is becoming increasingly evident in the literature that the sphingolipid metabolizing enzyme sphingosine kinase 1 (SKI) (E.C. 2.7.1.91) may act as an oncogene (Xia et al., 2000; Pitson et al, 2005; Vadas et al., 2008; Bergelin et al., 2009). Although most studies focus on the activation/upregulation of SKI, we are interested in the novel concept of SKI downregulation as a mechanism of tumor suppression. Our laboratory has previously shown that SKI proteolysis is p53 dependent in Molt-4 leukemia cells: inactivation of p53 inhibited SKI proteolysis after genotoxic stress (Taha et al., 2004). This review expands on this initial observation and is directed at exploring the p53-dependent regulation of sphingolipids and their metabolizing enzymes. Here, we provide background about the tumor suppressor p53 and discuss the currently known points of connection between the p53 and sphingolipid pathways, along with the therapeutic concept of tumor cell senescence.
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