Better Understanding the Role of p53 in Cancer

The gene p53 is an important tumor suppressor. A loss of function in p53 is involved in many cancers, permitting uncontrolled replication of cells. Here researchers make progress in understanding how this works under the hood, finding links that may help to provide a detail view of how rapamycin and a few other drugs act to reduce cancer risk.

The gene p53 has been described as the "guardian of the genome" due to its prominent role in preventing genetic mutations. More than half of all cancers are thought to originate from p53 mutations or loss of function. New research describes how mutations and or loss of function of the p53 gene activate a protein complex known as mammalian target of rapamycin complex 1 (mTORC1), which helps regulate the energy resources needed for cell proliferation.

mTORC1 is made up of several dozen proteins, and cells use the intracellular membranes of their lysosome as a scaffold to bring all of these proteins together. In response to the need of a normal cell, the p53 gene helps maintain proper levels of a protein known as tuberous sclerosis complex 2 (TSC2) in the lysosome. When p53 is not functioning properly, TCS2 levels in the lysosome drop, and a small protein known as RHEB takes its place. It is this accumulation of RHEB that activates mTORC1 and leads to the abnormal control of cell proliferation. "We have uncovered for the first time the signaling process that leads to excessive growth of cancer when p53 is lost. These protein interactions are like individual links in the chain of events leading to the development of cancer."

Link: http://www.eurekalert.org/pub_releases/2015-12/vcu-msu121415.php


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