title: p53 mutations change phosphatidylinositol acyl chain composition.
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.
authors.affiliation: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Naguib
authors.affiliation: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Gyula
authors.initials: G
authors.lastname: Bencze
authors.affiliation: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Dannielle D
authors.initials: DD
authors.lastname: Engle
authors.affiliation: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Iok I C
authors.initials: II
authors.lastname: Chio
authors.affiliation: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Tali
authors.initials: T
authors.lastname: Herzka
authors.affiliation: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Watrud
authors.affiliation: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Bencze
authors.affiliation: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Tuveson
authors.affiliation: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Darryl J
authors.initials: DJ
authors.lastname: Pappin
authors.affiliation: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA. Electronic address: trotman@cshl.edu.
authors.forename: Lloyd C
authors.initials: LC
authors.lastname: Trotman
mesh_terms: D002460:Cell Line; D005227:Fatty Acids / Q000378:metabolism*; D057166:High-Throughput Screening Assays; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D018129:Phosphatidylinositol Phosphates / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D015290:Second Messenger Systems / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D018129:Phosphatidylinositol Phosphates; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human