Exploring Protein Post-Translational Modifications of Breast Cancer Cells Using a Novel Combinatorial Search Algorithm

Abstract

Post-translational modification of proteins plays an important role in cancer cell biology. Proteins encoded by oncogenes may be activated by phosphorylation, products of tumour suppressors might be inactivated by phosphorylation or ubiquitinylation, which marks them for degradation; chromatin-binding proteins are often methylated and/or acetylated. These are just a few of the many hundreds of post-translational modifications discovered by years of painstaking experimentation and the chemical analysis of purified proteins. In recent years, mass spectrometry-based proteomics emerged as the principal technique for identifying such modifications in samples from cultured cells and tumour tissue. Here, we used a recently developed combinatorial search algorithm implemented in the MGVB toolset to identify novel modifications in samples from breast cancer cell lines. Our results provide a rich resource of coupled protein abundance and post-translational modification data seen in the context of an important biological function—the response of cells to interferon gamma treatment—which can serve as a starting point for future investigations to validate promising modifications and explore the utility of the underlying molecular mechanisms as potential diagnostic or therapeutic targets.