p53 and Apoptosis
Tumor protein 53, commonly referred to as Tp53 or p53, is an important protein for apoptosis. This master regulator has far reaching effects on apoptosis; it is capable of affecting both the intrinsic and extrinsic pathways. Control of tumor development is highly dependent on p53 monitoring cell proliferation. Because p53 mutations exist in approximately 50% of tumor cells, the importance of this protein is too great to ignore. p53 can be induced by internal and external stress signals, such as DNA damage, oxidative stress, loss of normal cellular contacts, and radiation.
The protein, encoded by the gene TP53, has been described as the 'guardian of the genome', in part for its central role in DNA repair. Mdm2, which determines the functionality of p53, must therefore be the 'master of the guardian'. Under normal circumstances, Mdm2 binds to p53 and through its inherent E3 ubiquitin ligase activity, ubiquitinates p53 at several sites in the center and carboxyl terminus (Figure 1). In addition, an unkown protein neddylates p53, adding ubiquitin-like Nedd8 to sites within the DNA binding domain (DBD) of p53. Other E3 ligases can also induce p53 ubiquitination. Consequently, p53 is targeted for proteolysis through the proteasome.
The Structure of p53
The 53 kDa calculated from gel migration is an illusion produced by a preponderance of prolines, hiding an actual mass of only 43.7kDa. In spite of this, a lot of information is packed into a mere 393 amino acids. Major domains include two activation domains (AD1, AD2), and a proline-rich domain (PRD) at the amino terminus, the large central DBD mentioned above, with an oligomerization domain (OD), and a Lys (K)-rich basic domain (BD) towards the carboxyl terminus.
p53 Gene Data
| Species | Gene Symbol | Gene Accession No. |
|---|---|---|
| Human | TP53 | NM_000546 |
| Mouse | Trp53 | NM_011640 |
| Rat | Tp53 | NM_030989 |
p53 Products
Inhibitors
| Cat.No. | Product Name | Activity |
|---|---|---|
| 2936 | NSC 66811 | MDM2 inhibitor. Disrupts MDM2-p53 interaction |
| 1267 | Pifithrin-α hydrobromide | p53 inhibitor. Also aryl hydrocarbon receptor agonist |
| 3843 | Cyclic Pifithrin-α hydrobromide | p53 inhibitor |
| 2653 | Pifithrin-μ | Inhibitor of p53-mitochondrial binding |
| 2443 | RITA | p53-MDM2 interaction inhibitor; antitumor |
Activators
| Cat.No. | Product Name | Activity |
|---|---|---|
| 3356 | WR 1065 | p53 activator. Also ROS scavenger |
Antibodies and Blocking Peptides
| Cat.No. | Product Name | Activity |
|---|---|---|
| 2366 | Anti-p14ARF (Clone 4C6/4) | Antibody recognizing p14ARF |
| 2376 | Anti-p53 (Clone DO-2) | Antibody recognizing p53 |
| 2378 | Anti-p53 (Clone pAB 1801) | Antibody recognizing p53 |
| 2375 | Anti-p53 (Clone pAB 1802) | Antibody recognizing p53 |
| 2369 | Anti-p53 (Clone pAB 240) | Antibody recognizing p53 |
Other
| Cat.No. | Product Name | Activity |
|---|---|---|
| 3023 | CP 31398 dihydrochloride | p53-stabilizing agent |
| 2185 | NSC 146109 hydrochloride | Cell-permeable, genotype-selective antitumor agent; activates p53-dependent transcription |
| 3710 | PRIMA-1MET | Restores mutant p53 activity |
| 3214 | RETRA hydrochloride | Antitumor agent; suppresses mutant p53-bearing cancer cells |
| 3365 | Tenovin-1 | Activates p53 transcriptional activity |
