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P53 DNA-binding domain P53 is a tumor suppressor gene product; mutations in p53 or lack of expression are found associated with a large fraction of all human cancers. P53 is activated by DNA damage and acts as a regulator of gene expression that ultimatively blocks progression through the cell cycle. P53 binds to DNA as a tetrameric transcription factor. In its inactive form, p53 is bound to the ring finger protein Mdm2, which promotes its ubiquitinylation and subsequent proteosomal degradation. Phosphorylation of p53 disrupts the Mdm2-p53 complex, while the stable and active p53 binds to regulatory regions of its target genes, such as the cyclin-kinase inhibitor p21, which complexes and inactivates cdk2 and other cyclin complexes. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",