One Function—Multiple Mechanisms: The Manifold Activities of p53 as a Transcriptional Repressor
Figure 5
Indirect repression through regulation of other target genes. Indirect repression mechanisms are characterised by complete absence of p53 at the target gene promoters. It binds neither at the promoter itself nor at the periphery through protein-protein interactions. p53 regulates expression of numerous transcription factors and changes in their expression should have an impact on their target genes, too (panel I). Furthermore, the CDK-Inhibitor p21CIP1 has been implicated in the repression mechanism of several genes (panel II). Increased expression of p21CIP1 protein due to p53-dependent transactivation leads to inhibition of several CDKs. Consequently the retinoblastoma protein remains hypophosphorylated. Hence, instead of releasing E2F which can act as a transcriptional activator, hypophosphorylated RB remains complexed with E2F and functions as a repressor.
