Objective       Post-translational modification of protein was the most important regulatory mechanism of cell protein in playing biological functions. This study aimed to research ubiquitination or neddylation associated proteins in tumor drug resistance.       Methods       We employed 1D SDS-PAGE and Chip HPLC-MS/MS to separate and identify ubiquitinated or neddylated proteins from the lysates of CDDP treated or untreated A549 and A549/CDDP cells. Western blotting and confocal laser scanning microscopy were used to validate those results. The sensitivity of cisplatin to cells was determined by MTT assay.       Results        A SUMO protein pyruvate kinase M2 (PKM2) was identified which located in the cytoplasm and nucleus. The expression of PKM2 was milder in the A549/CDDP cells than in A549 cells

but it was up-regulated when A549/CDDP cells were treated with proteasome inhibitors MG132. Drug resistance was decreased when the A549 and A549/CDDP cells were treated with CDDP combined with MG132.       Conclusion        The expression of PKM2 is negatively correlated with drug resistance in tumor cells. The expression of PKM2 is regulated by SUMO which was a neddylation modification

suggesting that PKM2 might be involved in the development of drug resistance.