Research: tumor suppressing protein associated with CHARGE syndrome -
CHARGE, which affects babies 1 to 10,000, is an acronym whose letters show up at some of the most common symptoms of the condition :. coloboma of the eye, heart defects, choanal atresia, retarded growth and / or development, genital and / or urinary abnormalities, and abnormalities of the ear and deafness
to originally, the researchers examined the tumor -suppressive properties of the protein, called p53, not to investigate developmental disorders. But when a mouse model developed a strange set of shortcomings, researchers followed a trail of clues that led them to bind p53 with CHARGE syndrome.
"It was a surprise and very intriguing," said Jeanine Van Nostrand, PhD, lead author of a paper describing the research and a former graduate student at Stanford, now at the Salk Institute for Biological Studies . "P53 has never been shown before to have a role in CHARGE."
The document will be published online Aug. 3 in Nature . The lead author is Laura Attardi, PhD, professor of radiation oncology and of genetics.
cellular quality control regulator
Researchers originally created a mouse model that expressed a mutated form of the protein, known as p53, p53 to investigate behavior in tumor suppression. Mice expressing only the mutated protein survived. But to their surprise, the heterozygous mice, or those with one copy of the mutated p53 and one normal copy, developed symptoms of LOAD and death in utero.
p53 is a cellular quality control regulator. When he sees a sick cell, it activates other proteins to kill the cell or stop its division. In a human being in development or mouse, other p53 proteins therefore extinguish it does not kill inadvertently important cells. The mutated form of p53 was created by researchers off off-switch, but it also may not communicate with other proteins to trigger cell death. Therefore, a mouse containing only mutated p53 survived to adulthood.
However, when the mice had a copy of a mutated p53 gene and one normal copy, hybrids formed resulting proteins. These hybrid proteins p53 could not be extinguished, but they retained the ability to trigger cell death. Interestingly, these proteins affected certain types of cells, causing symptoms of LOAD. The results suggest that p53 may play a role in other developmental disorders, Attardi said.
"It really reiterates how carefully p53 must be set," said Attardi. "It must be switched on at the right time and place. If it does not, it can cause damage."
CHARGE linked to a mutation of the gene
CHARGE mechanisms remain a mystery, although it has been linked to a mutation in a gene called CHD7. Attardi team examined the link between p53 and CHD7. They found that the CHD7 protein can keep p53 turned off.
In p53 binding with CHARGE, this study provides insight into the molecular pathways that could be used to develop therapies CHARGE, said co-author Donna Martin, MD, PhD, associate professor of pediatrics and human genetics at the University of Michigan Medical School and an expert on CHARGE.
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