P53: Difference between revisions

Joel L. Sussman (talk | contribs)
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In a normal cell, p53 is inactivated by its negative regulatory mdm2 (hdm2 in humans) and it is found at low levels. When DNA damage is sensed, p53's level rises. p53 binds to many regulatory sites in the genome and begins production of proteins that stop cell division until the damage is repaired. If the damage is irreparable, p53 initiates the process called programmed cell death, apoptosis, permanently removing the damage.  
In a normal cell, p53 is inactivated by its negative regulatory mdm2 (hdm2 in humans) and it is found at low levels. When DNA damage is sensed, p53's level rises. p53 binds to many regulatory sites in the genome and begins production of proteins that stop cell division until the damage is repaired. If the damage is irreparable, p53 initiates the process called programmed cell death, apoptosis, permanently removing the damage.  


In most cases of human cancer, p53 mutations have been observed. Most of the p53 mutations that may result in cancer are found in and around the DNA-binding surface of the protein. The most common mutation changes can be seen in a close up view of the <scene name='26/26327/B_chain_and_dna/5'>DNA binding domain with DNA </scene> color coded N to C (in rainbow colors), with the amino <scene name='26/26327/B_chain_and_dna/4'>R248</scene> (as space filling spheres) interacting with DNA. When mutated to another amino acid, this interaction is lost. Other residues associated with cancer-causing mutations are arginine <scene name='26/26327/B_chain_and_dna/8'>175, 249, 273, 282 and glycine 245</scene>.  Key residues associated with mutations are represented by magenta spheres.
In most cases of human cancer, p53 mutations have been observed. Most of the p53 mutations that may result in cancer are found in and around the DNA-binding surface of the protein. The most common mutation changes can be seen in a close up view of the <scene name='26/26327/B_chain_and_dna/5'>DNA binding domain with DNA </scene> color coded N to C (in rainbow colors), with the amino <scene name='26/26327/B_chain_and_dna/4'>R248</scene> (as space filling spheres) interacting with DNA. When mutated to another amino acid, this interaction is lost. Other residues associated with cancer-causing mutations are <scene name='26/26327/B_chain_and_dna/8'>175, 249, 273, 282 and glycine 245</scene>.  Key residues associated with mutations are represented by magenta spheres.




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There is a Zn-binding motif on p53. The p53 Zn atom is coordinated by residues
There is a Zn-binding motif on p53. The p53 Zn atom is coordinated by residues <scene name='26/26327/B_chain_and_dna/9'>C176, H179, C238, and C242</scene> that are located on two loops, respectively. It is conceivable that the zinc plays a role in stabilizing the two loops through
C176, H179, C238, and C242 that are located on two loops, respectively. It is conceivable that the
zinc plays a role in stabilizing the two loops through
coordination. The Zn has been represented as a red sphere in the figure at the right.
coordination. The Zn has been represented as a red sphere in the figure at the right.
</StructureSection>
</StructureSection>

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Eran Hodis, Mary Ball, David Canner, Joel L. Sussman, Michal Harel, Alexander Berchansky