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Disruption of Dnmt1/PCNA/UHRF1 Interactions Promotes Tumorigenesis from Human and Mice Glial Cells

Figure 5

pDnmt1S127/S143 and/or pDnmt1S127 catalyze low mMTase activity in comparison with Dnmt1/PCNA/UHRF1 and is hallmark associated with poor prognosis in glioma.

(A) Analysis of the mMTAse activity catalyzed by the Dnmt1, the Akt-mediated phosphorylation of the Dnmt1 (pDnmt1-PAS), the PKC-mediated phosphorylation of the Dnmt1 (pDnmt1-PPCS), in presence of equimolar quantity of PCNA, (Dnmt1-PCNA), or UHRF1 (Dnmt1-UHRF1) or PCNA and UHRF1 (Dnmt1-PCNA-UHRF1). mMTAse activities were assessed by DMB assay according to Yokochi and Robertson (2004). (B) Correlation study between the mMTase activity and the expression level of pDnmt1S127 and pDnmt1S143 harbored by 16 GBM. ○ represents grade IV astrocytomas/GBM. (C) Kaplan-Meier estimates time of survival between patients suffering from glioma presenting a high expression level of pDnmt1S127 and pDnmt1S143 (grey line) and those whose tumors harbored a low expression level of pDnmt1S127 and pDnmt1S143 (black line).

Figure 5

doi: https://doi.org/10.1371/journal.pone.0011333.g005