Another Key to the p53 DoorJuly 29, 2004Researchers at the Uppsala Branch of the Ludwig Institute for Cancer Research (LICR) have discovered that the transcription factor Yin Yang 1 (YY1) is a novel regulator of the tumor suppressor p53, which is inactivated in at least half of all human cancers. The p53 transcription factor plays a vital role in preventing cancer onset, by stimulating cells to commit suicide when their DNA is damaged by chemicals or UV exposure. Because YY1 prevents p53 from removing pre-cancerous cells, YY1 represents a hitherto unsuspected candidate for a source of p53-inactivating mutations, as well as a potential new target for future therapies. According to the study published today in the Proceedings of the National Academy of Sciences USA, YY1 regulates p53 at multiple levels. First, YY1 uses the novel mechanism of causing Mdm2, a key oncogene that marks proteins for degradation, to have an enhanced interaction with p53. This results in a decrease in the amount of p53 in the cell. YY1 also directly blocks p53's interaction with its cofactors, such that p53 can no longer act as a transcription factor to cause cell suicide in response to DNA damage. "In terms of possible therapies for the future, YY1's regulation of p53 at different levels means that we have new, different targeting options," says LICR's Dr. Johan Ericsson, the senior author of the study. "We know that we can use small molecules to prevent transcription factors from interacting with other proteins, so we can consider blocking YY1's direct interaction with p53 as a therapy option. We can also think about ways of disrupting the Mdm2 and YY1 interaction, and so prevent the indirect inhibition of p53." For now, Ericsson and his team are focused on investigating the growing body of evidence that suggests YY1 could be a pivotal transcription factor in cancer. "YY1 interacts with several transcription factors involved in cancer, for example, Myc and Notch, and now we know it also regulates p53," says Ericsson. "No-one has yet looked at mutations in YY1, but the fact that it is associated with so many proteins implicated in tumorigenesis, suggests to me that YY1 could be a lot more important than anyone ever realized." The present study continues a tradition of p53 research within LICR. The protein was discovered by Dr. Lloyd J. Old, the Director of LICR, in 1979. More recently, the ASPP family of proteins, which act to stimulate p53 activity in counter-balance to YY1, was discovered by Dr. Xin Lu, the Director-Designate of LICR's Branch at University College London, UK. | |||||||||||||||||||||
|
Related DNA Current Events and DNA News Articles Protein's essential role in repairing damaged cells revealed University of Michigan researchers have discovered that a key protein in cells plays a critical role in not one, but two processes affecting the development of cancer. Genetic mutation causes familial susceptibility for degenerative brain disease Mutation of a gene that helps proteins migrate in and out of the cell's genetic command center - the nucleus - puts some families at higher risk for the degenerative brain disease acute necrotizing encephalopathy (ANE). NYU scientists discover dangerous new method for bacterial toxin transfer Scientists have discovered a new way for bacteria to transfer toxic genes to unrelated bacterial species, a finding that raises the unsettling possibility that bacterial swapping of toxins and other disease-aiding factors may be more common than previously imagined. Plant polymerases IV and V are special forms of Polymerase II It's a little like finding out that Superman is actually Clark Kent. A team of biologists at Washington University in St. Louis has discovered that two vital cellular components, nuclear RNA Polymerases IV and V (Pol IV and V), found only in plants, are actually specialized forms of RNA Polymerase II, an essential enzyme of all eukaryotic organisms, including humans. Evolution in action: Our antibodies take 'evolutionary leaps' to fight microbes With cold and flu season in full swing, the fact that viruses and bacteria rapidly evolve is apparent with every sneeze, sniffle, and cough. A new report in the January 2009 issue of The FASEB Journal, explains for the first time how humans keep up with microbes by rearranging the genes that make antibodies to foreign invaders. This research fills a significant gap in our understanding of how the immune system helps us survive. Team finds breast cancer gene linked to disease spread A team of researchers at Princeton University and The Cancer Institute of New Jersey has identified a long-sought gene that is fatefully switched on in 30 to 40 percent of all breast cancer patients, spreading the disease, resisting traditional chemotherapies and eventually leading to death. Collagen VI may help protect the brain against Alzheimer's disease Scientists from the Gladstone Institute of Neurological Disease (GIND), UCSF, and Stanford have discovered that a certain type of collagen, collagen VI, protects brain cells against amyloid-beta (Aβ) proteins, which are widely thought to cause Alzheimer's disease (AD). Testes stem cell can change into other body tissues, Stanford/UCSF study shows Scientists at the Stanford University School of Medicine and at UC-San Francisco have succeeded in isolating stem cells from human testes. Understanding Extinct Microbes May Influence the State of Modern Human Health The study of ancient microbes may not seem consequential, but such pioneering research at the University of Oklahoma has implications for the state of modern human health. Cecil Lewis, assistant professor in the Department of Anthropology, says results of this research raise questions about the microbes living on and within people. In lung cancer, silencing one crucial gene disrupts normal functioning of genome While examining patterns of DNA modification in lung cancer, a team of international researchers has discovered what they say is a surprising new mechanism. More DNA Current Events and DNA News Articles |
|||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||