Figure 7.

Possible role of 14-3-3 in the p53 pathway. Upon stress signal, kinases are activated that phosphorylate p53 at multiple sites creating 14-3-3 binding motifs in vivo. p53 is stabilized against MDM2-mediated degradation by 14-3-3 τ and σ. Isoforms ε and γ modulate the transcriptional activity of p53 by stimulating sequence-specific DNA binding of p53. p53 is stabilized and activated for the transcription of target genes involved in cell-cycle arrest or apoptotic pathways. 14-3-3 σ is a target gene of p53 and is directly involved in cell-cycle arrest, inhibiting G2-M progression. Further, a positive feedback loop has been proposed for p53 and 14-3-3 σ (21,22).