P53 Mutations Change Phosphatidylinositol Acyl Chain Composition

Naguib, A., Bencze, G., Engle, D. D., Chio, II, Herzka, T., Watrud, K., Bencze, S., Tuveson, D. A., Pappin, D. J., Trotman, L. C. (2014) P53 Mutations Change Phosphatidylinositol Acyl Chain Composition. Cell Reports, 10 (1). pp. 8-19. ISSN 2211-1247

URL: http://www.ncbi.nlm.nih.gov/pubmed/25543136
DOI: 10.1016/j.celrep.2014.12.010

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.

Item Type: Paper
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > PTEN
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
CSHL Authors:
Communities: CSHL Cancer Center Program > Signal Transduction
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Animal Tissue and Imaging Service
CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL Cancer Center Shared Resources > Mass Spectrometry Service
CSHL Cancer Center Shared Resources > Microscopy Service
CSHL Cancer Center Shared Resources > Proteomics Service
CSHL labs > Pappin lab
CSHL labs > Trotman lab
CSHL labs > Tuveson lab
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User: Matt Covey
Date Deposited: 05 Jan 2015 16:47
Last Modified: 04 Nov 2015 20:29
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31020

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