Prions and cancer: A story unfolding

Prions, the causal agents of Mad Cow and other diseases, are very unique infectious particles. They are proteins in which the complex molecular three-dimensional folding process just went astray. For reasons not yet understood, the misfolding nature of prions is associated to their ability to sequester their normal counterparts and induce them to also adopt a misfolding conformation. The ever-growing crowd of misfolded proteins form the aggregates seen in diseases such as Parkinson's and Alzheimer's. Once misfolded, a protein can no longer exert its normal functions in the cell.

Now, a group led by Dr Jerson Lima Silva at the Federal University of Rio de Janeiro, Brazil, presents some new evidence that p53, a protein with the daunting task of suppressing tumor formation in the body, may show a typical prion-like behavior when mutated.

It has been known for some time that the buildup of p53 in the cell impairs the protein in preventing tumor growth. This has been observed in neuroblastoma, retinoblastoma, breast, and colon cancers. In a paper entitled "Mutant p53 aggregates into prion-like amyloid oligomers and fibrils: Implications for cancer" and published in the Journal of Biological Chemistry, the group shows that in cell lines carrying the most common , the formation of amyloid-like aggregates of p53 proteins may explain the protein's lack of function.

Whether this prionoid behavior in fact represents a relevant cancer-related mechanism remains to be shown. Development of novel and ingenious strategies to prevent p53 misfolding and aggregation may be just one way to find out.

"We are planning pre-clinical tests with synthesized in an attempt to prevent the changing in conformation of normal p53, and avoid aggregates of misfolded protein," says Dr. Silva.

If successful, the strategy may help unveil unforeseen leading to tumor development. Considering that more than half of the cancers lose p53 function, this prionoid behavior may serve as a potential novel target for cancer therapy, dramatically transforming our way of thinking of cancer and treating cancer patients.

More information: Journal of Biological Chemistry doi: 10.1074/jbc.M112.340638

Related Stories

Cancer is a p53 protein aggregation disease

date Mar 29, 2011

Protein aggregation, generally associated with Alzheimer's and mad cow disease, turns out to play a significant role in cancer. In a paper published in Nature Chemical Biology, Frederic Rousseau and Joost Schymkowitz of VIB ...

Drug kills cancer cells by restoring faulty tumor suppressor

date May 14, 2012

A new study describes a compound that selectively kills cancer cells by restoring the structure and function of one of the most commonly mutated proteins in human cancer, the "tumor suppressor" p53. The research, published ...

Cellular stress can induce yeast to promote prion formation

date Jul 23, 2011

It's a chicken and egg question. Where do the infectious protein particles called prions come from? Essentially clumps of misfolded proteins, prions cause neurodegenerative disorders, such as mad cow/Creutzfeld-Jakob disease, ...

Recommended for you

Spicy treatment the answer to aggressive cancer?

date 3 hours ago

It has been treasured by food lovers for thousands of years for its rich golden colour, peppery flavour and mustardy aroma…and now turmeric may also have a role in fighting cancer.

Cancer survivors who smoke perceive less risk from tobacco

date 20 hours ago

Cancer survivors who smoke report fewer negative opinions about smoking, have more barriers to quitting, and are around other smokers more often than survivors who had quit before or after their diagnosis, according to a ...

Melanoma mutation rewires cell metabolism

date 20 hours ago

A mutation found in most melanomas rewires cancer cells' metabolism, making them dependent on a ketogenesis enzyme, researchers at Winship Cancer Institute of Emory University have discovered.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.