Researchers discover a new function of the most important tumor suppressor protein body -
Cold Spring Harbor Laboratory Researchers (CSHL) have discovered a new function of most important tumor suppression protein body. p53 called, this protein has been called the "guardian of the genome". It normally comes to the fore when healthy cells feel damage to their DNA caused by stress, such as exposure to toxic chemicals or intense exposure to UV rays. If the damage is severe, p53 can cause cell to commit pre-programmed cell death or apoptosis. Mutant versions of the p53 performing over this vital function, on the other hand, are catalysts of many different cancers.
researcher Dr. Raffaella Sordella cancer, CSHL associate professor, and his colleagues report today in Proceedings of the National Academy of Sciences discovering a cousin p53-p53 they call psi (Greek letter "psi"). It is a previously unknown variant of the p53 protein, generated by the same gene, called TP53 in humans, which leads to other forms of p53.
Sordella and his colleagues observed that p53 psi, when expressed reduces the expression of a molecular glue called E-cadherin, which normally keeps contacting the cells in epithelial tissue the tissue that forms the lining of the lung and other organs. This is accompanied by the expression of key cellular markers associated with the invasiveness of the tumor and its metastatic potential. (These are markers of EMT, or epithelial-mesenchymal transition.) Invariably Sordella and his team found levels of p53-psi to be elevated in tumors in the early stages of lung poor prognosis.
A thorough investigation revealed that p53-psi generates favorable effects on growth by interacting with a protein called cyclophilin D (CypD), the membrane of the energy factories of the cell, the mitochondria, and by stimulating the production of oxidizing molecules called reactive oxygen species (ROS).
p53-psi was found by the team to be inherently expressed in tumors, but also in the damaged tissues. "This is interesting," Sordella said, "because the generation of cells characteristic of those observed in the healing of wounds with previously seen in tumors."
It is possible, Sordella said most familiar p53 mutants associated with tumor growth and metastasis can have "hijacked" the capacity of the program used by p53-psi; to promote healing in tissue damage. A cell program, ie which has evolved over eons to heal may have been hijacked by mutant p53 to enable cancers to spread out of control.
The team is currently studying p53-psi in healing to help clarify its role. Confirmation would give support to the theory that the misappropriation of mutant p53 that work to help advance pro-metastatic process in cancer.
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