Disruption of Dnmt1/PCNA/UHRF1 Interactions Promotes Tumorigenesis from Human and Mice Glial Cells
Figure 3
The disruption of the Dnmt1/PCNA/UHRF1 interactions is associated with the phsphorylation of Dnmt1 by Akt and/or PKC.
(A) Visualization, in primary cultured tumor cells (PCTC) of different grade of glioma, of the phosphorylation level of Dnmt1 by using antibodies recognizing the phospho-(Ser/Thr) Akt substrate (pDnmt1-PAS, Ozyme, Cell Signal#9614, France) and the the phospho-(Ser) PKC substrate (pDnmt1-PPCS, Ozyme, Cell Signal#2261, France). (B) Effect of the Akt and PKC inhibition on the phosphorylation level of Dnmt1, the Dnmt1-PCNA-UHRF1 interactions and on the mMTAse activity. (Akti: 0.1 µM Calbiochem#124005, France; PKCi or Go6893, 0.5 µM Calbiochem#124005, France). (C) Effect of the constitutive activation of Akt and PKC in Ntv-a/PDGF cells on the phosphorylation level of Dnmt1, the Dnmt1-PCNA-UHRF1 interactions and on the mMTAse activity.