Fig. 7.

Model for the regulation of PRMT5 expression by the PKC-c-Fos-NF-Y signaling in human cancer. (A) The PKC signaling negatively regulates PRMT5 expression in a c-Fos- and NF-Y-dependent manner in LNCaP cells. In response to PMA treatment, activation of PKC leads to the induction of c-Fos, which in turn suppresses NF-YA transcription and results in down-regulation of PRMT5. As a result, cell growth is inhibited. (B) Proposed mechanisms underlying up-regulation of PRMT5 expression in cancer cells. Two possible mechanisms may underlie PRMT5 overexpression in human cancers. One is the inactivation or down-regulation of PKC by cell signaling, and the other is direct activation or up-regulation of NF-YA by cell signaling that remains to be identified (X). Dashed lines indicate unknown factors that remain to be identified. Thick solid arrows illustrate the up-regulation or down-regulation of the indicated protein.