Fig. 7. A novel transcriptional activation pathway of c-MYC by OCT4 phosphorylated by MK2.
a c-MYC, OCT4, phosphoOCT4 (pOCT4S111), MK2, and phosphoMK2 (pMK2T334) expression in patient-derived xenografts (PDXs) of neuroblastoma established from clinical samples of obtained at diagnosis (n = 8) and at progressive disease (n = 9). CHLA-20 was used as the control for the two membranes. * COG-N-603x and COG-N-623x are matched Dx-PD pair of PDXs established from the same patients. The matched-pair direct-to-culture cell lines are COG-N-603h and COG-N-623h shown in Fig. 5g. b Dot plots quantitating immunoblotting data from a. The values were normalized in two ways by the expression of specific proteins in CHLA-20 and GAPDH. c Correlation between c-MYC and pOCT4S111, c-MYC and pMKT334, and pOCT4S111 and pMKT334. The results of linear regression analyses with 95% confidence interval (dotted line) are presented (n = 17). d Proposed mechanism of c-MYC transcriptional activation in progressive disease neuroblastoma. MK2 shuttles into the nuclei of cells and phosphorylates OCT4 at S111 residue. There are two OCT4-binding sites in the c-MYC promoter/enhancer region between −1209 and −1140. The binding of pOCT4S111 increases transcriptional activation of MYC.