P53: Difference between revisions
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p53 Tumor Suppressor | p53 Tumor Suppressor | ||
[[Image:p53-unbound.gif|right]] | [[Image:p53-unbound.gif|right|400px]] | ||
==Guardian of the Cell== | ==Guardian of the Cell== | ||
Our cells face many dangers, including chemicals, viruses, and ionizing radiation. If cells are damaged in sensitive places by these attackers, the effects can be disastrous. For instance, if key regulatory elements are damaged, the normal controls on cell growth may be blocked and the cell will rapidly multiply and grow into a tumor. p53 tumor suppressor is one of our defenses against this type of damage. p53 tumor suppressor is normally found at low levels, but when DNA damage is sensed, p53 levels rise and initiate protective measures. p53 binds to many regulatory sites in the genome and begins production of proteins that halt cell division until the damage is repaired. Or, if the damage is too severe, p53 initiates the process of programmed cell death, or apoptosis, which directs the cell to commit suicide, permanently removing the damage. | Our cells face many dangers, including chemicals, viruses, and ionizing radiation. If cells are damaged in sensitive places by these attackers, the effects can be disastrous. For instance, if key regulatory elements are damaged, the normal controls on cell growth may be blocked and the cell will rapidly multiply and grow into a tumor. p53 tumor suppressor is one of our defenses against this type of damage. p53 tumor suppressor is normally found at low levels, but when DNA damage is sensed, p53 levels rise and initiate protective measures. p53 binds to many regulatory sites in the genome and begins production of proteins that halt cell division until the damage is repaired. Or, if the damage is too severe, p53 initiates the process of programmed cell death, or apoptosis, which directs the cell to commit suicide, permanently removing the damage. | ||
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==Structures by Parts== | ==Structures by Parts== | ||
p53 tumor suppressor is a flexible molecule composed of four identical protein chains. Flexible molecules are difficult to study by x-ray crystallography because they do not form orderly crystals, and if they do crystallize, the experimental images are often blurry. | <applet load='1olg' size='400' frame='true' align='left' />p53 tumor suppressor is a flexible molecule composed of four identical protein chains. Flexible molecules are difficult to study by x-ray crystallography because they do not form orderly crystals, and if they do crystallize, the experimental images are often blurry. So, p53 has been studied in parts, by removing the flexible regions and solving structures of the pieces that form stable structures. Three of these compact, globular portions, termed "domains", have been studied. At the center of p53 is a tetramerization domain (PDB entry [[1olg]]) that ties the four chains together. A long flexible region in each chain then connects to the second stable domain: a large DNA-binding domain (PDB entry [[1tup]]) that is rich in arginine residues that interact with DNA. This domain recognizes specific regulatory sites on the DNA. The third stable domain studied thus far is the transactivation domain (PDB entry [[1ycq]]), found near the end of each arm, that activates the DNA-reading machinery. | ||
==p53 and Cancer== | ==p53 and Cancer== | ||