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European Biopharmaceutical Review

Redefining Proteomics

Tumour suppressor p53 (TP53) is a gene, not a protein. It is rhetorically convenient but scientifically inaccurate to suggest these are morphological variants of the same thing. Human cells splice and assemble in at least nine different ways the exons present in the TP53 gene. Therefore, TP53 isoform 7 is the appropriate name for an mRNA intermediary between gene and protein. Likewise, protein does not simply swap ribonucleotides for amino acids at a 3:1 ratio.

Many residues will be variously and reversibly modified with chemical, carbohydrate, lipidatious, and/or proteinacious adducts that will impart different structures and biochemical properties; direct the protein to different locations; alter activities, functions, and interactions; and control destruction of the molecule itself – all as the larger cell sees fit. These co- and post-translational modifications (PTM) are essential to everything about proteins that makes them so. Methylated, phospho-TP53 isoform 7 is thus a protein. If a proteomic screen is not providing this level of information, is it technically even proteomic?

Mass Spectrometry: Necessary but Insufficient

Stable proteins may have no concurrently existing, corresponding mRNA. Post-transcriptional regulation means not all mRNA present within cells has such corresponding protein. To identify the protein components of a complex sample, no substitute for mass spectrometry (MS) exists, particularly in targeted approaches where one seeks to identify the presence of a particular component within complex mixtures

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Dr Christian Loch is Chief Executive and Science Officer at AVMBioMed. He is also adjunct faculty in the Department of Chemistry at Villanova University, US, where he teaches proteomics in the graduate school. Christian has 10 years of industry experience and holds an MPH in epidemiology from the University of Washington, US, and a PhD in biochemistry from the University of Virginia, US.
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Dr Christian Loch
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