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P53 protein

== Introduction ==

	Cancer is one of the most popular diseases occurring today. Research has been done on this issue for an extended amount of years to figure out how this devastating case works and what factors are contributing to this devastating illness. Throughout time there have been some successful answers while some things still remain in question during this existent investigation. One of the most interesting roles in the fight with cancer happens to be a protein quite phenomenal to cell life. This protein is none other than the unique p53 protein. P53 protein is  a DNA binding protein and is an extremely important system in cell cycle control and the area of cancer. This protein was researched by Bert Vogelstein, David Lane, and Arnold Levine. The p53 protein is also called the guardian of the genome because of the role it has in checkpoint pathways of the cell cycle. This protein is located on chromosome 17 on the short arm which is where the open reading frames occur for proteins. The p53 protein was discovered through co-purification with a large T antigen in SV40 virus transformed cells.

Structure

The structure of the p53 protein is interestingly unique. This protein has a single polypeptide chain divided into three discrete domains, which show a structure that has facilitated study in the absence of the rest of the protein. These domains have been found to be a concern with tetramerization, transcriptional activation, and DNA binding. This protein has two ligands and two polymers. In the p53 protein a N-terminal transactivation domain extends from residues 1-99 and is followed by the central core region, the largest domain, which contains residues 100-300 that bind specific DNA sequences. The third region of this protein is the C-terminal domain from residues 301-393, which includes a regulatory region and a tetramerization domain. This is the . These are the main three domains described for this protein, it has been disputed that there are four domains instead of three. Discrete domains are linked by flexible linkers creating a molecule with dynamic conformation. The p53 protein has been found to be difficult to crystallize when in the form of its full length. The p53 protein is a β sandwich formed by the interaction of antiparallel four and five stranded elements of the β sheet.

Function

      The p53 protein is a tumor suppressor gene that stops the formation of tumors, particularly tumors that can lead to cancer. In order for the p53 protein to work it has to be phosphorylated. When DNA has double-stranded breaks, its altered form triggers the activation of the ataxia telangiectasia mutated (ATM) protein kinase. The ATM enzyme catalyzes the phosphorylation of checkpoint kinases within the cycle, which as a result phosphorylate the p53 protein. Phosphorylating the p53 protein in this manner helps protect it from degradation allowing it to buildup in the presence of damaged deoxyribonucleic acid (DNA). Now that p53 is available it can carry out its task in the cell cycle.
      The function of the p53 protein once it has accumulated includes cell cycle arrest in the G1 phase of the cycle and cell death. These events involve p53 binding to DNA and acting as a transcription factor which stimulates transcription of specific genes. 
      In cell cycle arrest, the p53 protein binds to DNA activating the transcription of the gene that codes for a Cdk inhibitor known as p21. The p53 protein causes inhibition of the p21 protein preventing phosphorylation of the Rb protein. This results in cell cycle arrest at the restriction point. 

The other event which involves the p53 protein is cell death. This process occurs when the damage DNA is unable to be repaired of an error. As a result the p53 protein activates genes coding for a group of proteins which use apoptosis to trigger cell death. However p53 does have an aid in completing this event successfully by working along with the p53 upregulated modulator of apoptosis (called Puma for short), which binds to and inactivates the Bcl-2 protein and promotes apoptosis.

      In order for any of these processes to occur it is very important that p53 is phosphorylated to avoid degradation. Phosphorylating the p53 protein will prevent it from interacting with the Mdm2 protein, which if allowed will link p53 to ubiquitin marking it for destruction by the proteasome.