p53

p53, Protein 53, Tumor Protein 53, Cellular Tumor Antigen p53

p53 is a transcription factor, also known as protein 53 or tumor protein 53 or cellular tumor antigen p53. The TP53 gene on chromosome 17 encodes p53.

p53 Name and Molecular Mass

- called p53 due to its molecular mass of 53 kilodaltons, 53 kDa, when run on SDS-PAGE

- actual weight should be around 44 kDa, but runs slower on SDS-PAGE due to high number of proline residues

p53 Structure

- 393 amino acids

- 7 domain protein

- nuclea localization signaling domain

- homo-oligomerisation domain

- DNA-binding core domain

- two activation domains (AD)

- proline rich domain

- down-regulation domain

p53 Function

- regulates cell cycle acting as a tumor suppressor, prevenitng cancer through halting the cell cycle if DNA damage is present

- confers DNA stability, thereby preventing DNA mutations

- therefore, nicknamed "guardian of the genome" and "the guardian of the genome"

- p53 can activate apoptosis, programmed cell death, if the DNA of cell is beyonded repair

- p53 can activate DNA repair proteins

- p53 can hold the cell cycle at G1/S regulation point, giving the DNA repair proteins time to repair the DNA

p53 Regulation

- normally, p53 levels are kept low throught the protein Mdm2

- Mdm2 binds p53 and moves it to the cytosol from the nucleus

- proteasomes degrade p53 in the cytosol

- activation of p53 is through phosphorylation of the N-terminal domain

- phosphorylation prevents Mdm2 from binding to p53 and moving it to the cytosol

- phosphorylated by protein kinases which have been activated by cellular stresses

- cell stresses that activate these protein kinases include but are not limited to DNA damage by UV light or oxidative stress

- MAPK family pathway mainly involved

- MAPK family includes ERK1, ERK2, p38 MAPK, JNK1, JNK2, JNK3

- in addition to MAPK, many other protein kinase pathways such as ART, ATM, CAK, can regulate p53

p53 and Cancer

- inherited mutations in p53 lead to Li-Fraumeni syndrome

- the great majority of human tumors, over 50%, harbor mutations or deletions in the TP53 gene, leading to abnormal production or levels of the p53 protein