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Surprise discovery links cancer protein with developmental disorder


Scores of scientific discoveries — including dynamite, penicillin, and heaps of others — were accidents. Fiddling around in the lab and wa-zam, there’s a cure for syphilis.

The same sort of thing happened recently in the Stanford lab of Laura Attardi, PhD, professor of radiation oncology and genetics. Her team studies the protein p53, a key tumor suppressor. Normally, when switched on, p53 tells other proteins to kill ailing cells — a critical role to keep cancer in check.

To investigate its behavior in an organism, the researchers created a mouse with a mutated form of p53. This mutated protein had no off switch, but it also couldn’t communicate with its “minion” proteins that kill cells, so when a mouse had two copies of the mutated protein, it survived. A mouse with two normal copies of p53 also survived.

But surprisingly, when researchers created a mouse with one copy of the mutated p53, and one normal copy, it died before birth. What was going on?

To figure it out, Jeanine Van Nostrand, PhD, a former Stanford graduate student, now a researcher at The Salk Institute for Biological Studies, tried to figure out exactly why the mice were dying. They also had a unique set of problems — inner and outer ear deformities, heart abnormalities and a rare gap in the eye among others. After consulting with developmental experts, the researchers linked the mice deaths to CHARGE syndrome, a rare developmental disorder that causes eye, ear, nasal and genital problems, among other symptoms. “It was a very big surprise and very intriguing,” Van Nostrand comments in a release. “P53 had never before been shown to have a role in CHARGE.”

The researchers learned the mice with one normal p53, and one mutant p53, had hybrid p53 proteins, Frankenstein-like molecules that lacked an off switch, but retained the ability to trigger cell death.

These proteins led to the CHARGE symptoms. And thanks to the study, which appeared online yesterday in Nature, researchers can use the new clues about CHARGE to begin developing potential therapies, said Donna Martin, MD, PhD, associate professor of pediatrics and genetics at the University of Michigan Medical School, a CHARGE expert and co-author of the paper.

Becky Bach is a former park ranger who now spends her time writing, exploring, or practicing yoga. She’s currently a science writing intern in the medical school’s Office of Communication & Public Affairs.

Photo of Attardi by Steve Fisch

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