Subcellular Relocalization of Proteins in Response to Cisplatin-Induced DNA Damage

Cells regulate the intracellular localization of proteins to adapt to different environmental conditions including DNA damage, but this form of regulation has not been analyzed systematically. The aim of this study was to investigate the protein distribution between nucleus and cytoplasm in response to cisplatin treatment. SKOV3 cells were treated or untreated with cisplatin in concentration 40 µM for 24 h followed by mass spectrometry-based proteomic analysis of extracts of cytoplasmic and nuclear fractions. To validate the quality of separation of the nuclear and cytoplasmic fractions, abundance of proteins, which are often used as markers of nuclear fraction (lamin B1 and RPA194), was evaluated using mass spectrometry. A total of 4,085 proteins were identified. Among them, 442 proteins were up-regulated, and 578 proteins were down-regulated in the nuclear fraction after cisplatin treatment. Interestingly, according to our data, after treatment of cells with cisplatin, spliceosomal proteins significantly increased in the cytoplasmic fraction. This indicates the relocalization of spliceosomal proteins from the nucleus into the cytoplasm under the influence of therapeutic stress.