Abstract
Relatively little attention has been paid to ADP-ribosylated modifications of histones, especially to mono-ADP-ribosylation. As an increasing number of mono-ADP-ribosyltransferases have been identified in recent studies, the functions of mono-ADP-ribosylated proteins have aroused research interest. In particular, histones are substrates of some mono-ADP-ribosyltransferases and mono-ADP-ribosylated histone have been detected in physiological or pathological processes. In this research, arginine-117 (Arg-117; R-117) of hsitone3(H3) is identified as the a site of mono-ADP-ribosylation in colon carcinoma(the first such site to be identified); this posttranslational modification may promote the proliferation of colon carcinoma cells in vitro and in vivo. Using a point-mutant lentivirus transfection and using an activator of P300 allowed us to observe the mono-ADP-ribosylation at H3R117 and enhancement of the activity of P300 to up-regulate the level of acetylated β-catenin, which could increase the expression of c-myc and cyclin D1.
Highlights
Epigenetics are widely reported to play a major role in early stages of neoplastic development and in the whole process of progression of cancer [1]
Our previous studies have shown that ART1 is associated with apoptosis, proliferation and migration of colon carcinoma CT26 cells [19, 23, 24]
We employed LC-MS/MS to analyze the site of mono-ADP-ribosylated modification on histone3 in different malignant cell lines and were pleased to find that this histone is mono-ADP-ribosylated only in the highly malignant colon carcinoma cell line (LOVO cells)
Summary
Epigenetics are widely reported to play a major role in early stages of neoplastic development and in the whole process of progression of cancer [1]. Compared with the early focus on the DNA as a critical epigenetic marks in progression of cancer, a growing body of research pays attention to the function of histone modifications in tumourigenesis [2]. Modifications of histones include acetylation, phosphorylation, methylation, ADP-ribosylation, ubiquitylation and sumoylation, amongst which acetylation of histones has already been confirmed in the regulation of various cancers. There is strong evidence that shows that poly-ADP-ribosylation of histones plays important roles in repair and replication of DNA [8, 9] and in proliferation of cells and tumors [10]. Research data on the role of mono-ADP-ribosylation in physical or pathological process are lacking to date
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