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Describe the structure and regulation of the p53 protein.
StructureHuman p53 is 393 amino acids long and has seven domains:
1. An acidic N-terminus transcription-activation domain (TAD), also known as activation domain 1 (AD1), which activates transcription factors: residues 1-42. The N-terminus contains two complementary transcriptional activation domains, with a major one at residues 1–42 and a minor one at residues 55–75, specifically involved in the regulation of several pro-apoptotic genes.
2. Activation domain 2 (AD2) important for apoptotic activity: residues 43-63.
3. Proline rich domain important for the apoptotic activity of p53: residues 64-92.
4. Central DNA-binding core domain (DBD). Contains one zinc atom and several arginine amino acids: residues 102-292. This region is responsible for binding the p53 co-repressor LMO3.
5. Nuclear localization signaling domain, residues 316-325.
6. Homo-oligomerisation domain (OD): residues 307-355. Tetramerization is essential for the activity of p53 in vivo.
7. C-terminal involved in downregulation of DNA binding of the central domain: residues 356-393.
FunctionP53 has many mechanisms of anticancer function, and plays a role in apoptosis, genomic stability, and inhibition of angiogenesis. In its anti-cancer role, p53 works through several mechanisms:
- It can activate DNA repair proteins when DNA has sustained damage.
- It can arrest growth by holding the cell cycle at the G1/S regulation point on DNA damage recognition (if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to continue the cell cycle).
- It can initiate apoptosis, the programmed cell death, if DNA damage proves to be irreparable.
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