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

add to favorites email to friend print save as pdf

Related Stories

Cancer is a p53 protein aggregation disease

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

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

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

Dog's epigenome gives clues to human cancer

1 hour ago

The bond between humans and dogs is strong and ancient. From being the protector of the first herds in a faithful pet, dogs and people share many aspects of life. The relationship between the two species ...

Study pinpoints microRNA tied to colon cancer tumor growth

16 hours ago

Researchers at the University of Minnesota have identified microRNAs that may cause colon polyps from turning cancerous. The finding could help physicians provide more specialized, and earlier, treatment before colon cancer ...

User comments