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Objective Protein acetylation and succinylation have gradually showed their importance in cancer investigation.The similarity in protein sites and regulation enzymes of these two modifications make it necessary to investigate them together.However,there lacks related studies in breast cancer.We systematically studied these two modifications of all proteins in human breast cancer tissues to investigate the correlation between protein acetylation and succinylation,as well as to identify potential targets.Methods Acetylome and succinylome technique were firstly used to detect and compare the protein modification levels in breast cancer and para-carcinoma normal tissues; Then a serious of bioinformatics analysis such as GO,Pathway and Venn analysis were executed to analyze the correlation and function of modified proteins and to screen potential targets; Finally,biological experiments such as Western-blot and RT-PCR were used to verify the proteomic results,HDAC and SIRT inhibitors were utilized to screen the potential regulators of protein acetylation and succinylation.Results About 60%modified proteins and sites were highly acetylated and succinylated in breast cancer tissues and the repetition rate between these two kinds of modified proteins was about 40%.Acetylated and succinylated proteins occupied a similar percentage in each function domain and both of them could exert their function mainly in glycolysis pathway,in which the key ATP catalysis enzyme PGK1 was significantly acetylated and succinylated.Further experiment results proved that PGK1 was overexpressed and highly modified in breast cancer cells when compared with normal cells.In addition,HDAC and SIRT inhibitor could increase the acetylation and succinylation level of PGK1 respectively.Conclusions Proteins in breast cancer were highly acetylated and succinylated and these two modified proteins showed a similarity in protein kinds and functions.The modified proteins may play important role in glycolysis pathway and PGK1 may be a potential target because of its overexpression and highly modification levels in breast cancer,as well as its key function in catalyzing ATP production.The acetylation and succinylation of PGK1 may be regulated by HDAC and SIRT family members respectively.