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CLICK IMAGE FOR MORE INFORMATIONHDM2, the human version of mouse MDM2 is a protein that negatively regulates the TP53 tumor suppressor protein. HDM2/MDM2 is one of a family of proteins in the ubiquitin proteolytic pathway that regulate proteins by targeting them for degradation. HDM2/MDM2 binds to and inactivates TP53, which is a tumor suppressor that causes growth arrest when cells suffer trauma or DNA damage. Growth arrest allows cells to repair their DNA prior to resuming growth. In some cancers, HDM2/MDM2 is genetically altered, causing production of more HDM2/MDM2 than is normally in cells. This abundance of HDM2/MDM2 binds to TP53, inducing its degradation, and without TP53, the cell cannot stop growing to repair damaged DNA before continuing to divide. Cell division that continues despite damaged DNA is more likely to lead to cancer.
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HDM2, the human version of mouse MDM2 is a protein that negatively regulates the TP53 tumor suppressor protein. HDM2/MDM2 is one of a family of proteins in the ubiquitin proteolytic pathway that regulate proteins by targeting them for degradation. HDM2/MDM2 binds to and inactivates TP53, which is a tumor suppressor that causes growth arrest when cells suffer trauma or DNA damage. Growth arrest allows cells to repair their DNA prior to resuming growth. In some cancers, HDM2/MDM2 is genetically altered, causing production of more HDM2/MDM2 than is normally in cells. This abundance of HDM2/MDM2 binds to TP53, inducing its degradation, and without TP53, the cell cannot stop growing to repair damaged DNA before continuing to divide. Cell division that continues despite damaged DNA is more likely to lead to cancer.
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Genetic amplification of HDM2/MDM2 means that the segment of DNA that encodes HDM2/MDM2 has been replicated several times, so that there are multiple copies of the gene in the tumor cells. Multiple copies mean that the gene is transcribed more than the normal amount it would be were there only one copy of the gene. This additional transcription of HDM2/MDM2 results in higher than normal levels of the HDM2/MDM2 protein in cells. Since HDM2/MDM2 protein functions to destroy TP53, TP53 levels in the cell drop drastically. This leaves the cells unable to stop growing in response to DNA damage or other signals that would normally trigger TP53 to cause cell cycle arrest.
Genetic amplification of HDM2/MDM2 means that the segment of DNA that encodes HDM2/MDM2 has been replicated several times, so that there are multiple copies of the gene in the tumor cells. Multiple copies mean that the gene is transcribed more than the normal amount it would be were there only one copy of the gene. This additional transcription of HDM2/MDM2 results in higher than normal levels of the HDM2/MDM2 protein in cells. Since HDM2/MDM2 protein functions to destroy TP53, TP53 levels in the cell drop drastically. This leaves the cells unable to stop growing in response to DNA damage or other signals that would normally trigger TP53 to cause cell cycle arrest.