However, in ER-negative cells where PPM1A expression is low, CDKs are not dephosphorylated, and the phosphorylated form of CDK6 phosphorylates RB, which causes the release of E2F, allowing it to bind DNA and induce transcription of E2F-regulated genes, ultimately stimulating tumor growth (Fig. 6). This evidence concerns the gene RB1 and neoplasm.