Regulation and Functions of the p53 Protein

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p53 gene, also known as tumor protein 53 (TP53), encodes for a tumor suppressor protein which regulates the cell cycle and apoptosis. The p53 protein has been described as the guardian of the genome (1) because of its role in preventing genetic mutation. It belongs to a protein family which includes p53, p63 and p73 and these are structurally and functionally related to each other. However, p53 seems to have evolved as a tumor suppressor in higher organisms, while p63 and p73 play a role in normal developmental biology (2).

Structure of p53
P53 functions primarily as a transcription factor, and is biologically active as a homo-tetramer comprising of 4 X 393 amino acid residues. Each monomer comprises of several functional domains:
1. An acidic N-terminus transcription-activating domain 1 and 2 (TAD1/2) - This region interacts with various transcription factors
2. Proline-rich region (PRR) - This plays a role in p53 stability
3. Central DNA binding domain (DBD) - required for binding to specific sites on the DNA.
4. Tetramerization domain (OD) - required for the assembly of the functional tetramer.
5. Carboxyl terminus domain (CTD) - which is bound to DNA binding domain and is involved in negative modulation of DNA binding domain.

The central DNA binding domain is the most highly conserved region of p53, when compared to its other family members, p63 and p73. Loss of tumor suppressor function of p53, as seen in most cancers, results from missense mutations in the DNA
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