ING Genes Work as Tumor Suppressor Genes in the Carcinogenesis of Head and Neck Squamous Cell Carcinoma
Figure 2
The role of p3 protein in tumor supression. p3 could recognize trimethylated lysine 4 of histone H3 (H3K4me3) by PHD domain and has been implicated in chromatin remodeling and activation of some genes transcription. This binding is somehow necessary for induction of DNA repair and cell death. p3 also associates with the Sin3/HDAC-mediated transcriptional repression through its unique N-terminal sequence and may be involved in repression of some essential cell cycle regulator genes. Moreover, p3 binds PCNA and p300 complex to promote DNA repair through a PIP motif in response to UV-irradiation and, subsequently, may trigger apoptosis by the induction of p21 expression. p3 competes with murine double minute 2 (MDM2) leading to an increase in the stability and activity of p53. p21, the one of the targets of p53, is also upregulated to involve in cell cycle arrest and the induction of apoptosis. Additionally, p3 could upregulate expression of HSP70 gene to induce apoptosis independently of p53 status. Furthermore, p3 binds to lamin A via LID domain to stabilize its level and biological function in nucleus. Conversely, 14-3-3 can bind to p3 with phosphorylated serine 199 and results in translocation of p3 from the nucleus to the cytoplasm, which may involve in tumorigenesis.
