Naguib, A., Bencze, G., Engle, D. D., Chio, II, Herzka, T., Watrud, K., Bencze, S., Tuveson, D. A., Pappin, D. J., Trotman, L. C. (December 2014) P53 Mutations Change Phosphatidylinositol Acyl Chain Composition. Cell Reports, 10 (1). pp. 8-19. ISSN 2211-1247
Abstract
Phosphatidylinositol phosphate (PIP) second messengers relay extracellular growth cues through the phosphorylation status of the inositol sugar, a signal transduction system that is deregulated in cancer. In stark contrast to PIP inositol head-group phosphorylation, changes in phosphatidylinositol (PI) lipid acyl chains in cancer have remained ill-defined. Here, we apply a mass-spectrometry-based method capable of unbiased high-throughput identification and quantification of cellular PI acyl chain composition. Using this approach, we find that PI lipid chains represent a cell-specific fingerprint and are unperturbed by serum-mediated signaling in contrast to the inositol head group. We find that mutation of Trp53 results in PIs containing reduced-length fatty acid moieties. Our results suggest that the anchoring tails of lipid second messengers form an additional layer of PIP signaling in cancer that operates independently of PTEN/PI3-kinase activity but is instead linked to p53.
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