MEMPHIS, Tenn., Sept. 13 /PRNewswire-USNewswire/ — St. Jude
Children’s Research Hospital investigators have identified a novel
structure in cells that serves as a control switch in the body’s
system for eliminating damaged cells and also offers new
therapeutic potential.
The findings provide fresh insight into the machinery at work as
cells ramp up production of p53 protein following DNA damage. The
p53 protein plays a critical role in how cells respond to the
stress that damages DNA. The gene that carries instructions for
making p53 protein is the most commonly mutated gene in human
cancers.
Investigators also identified molecules that disrupt the system
and reduce p53 protein levels in cells damaged by irradiation or
chemotherapy. These small molecules helped cells growing in the
laboratory survive better after they were damaged. The findings
appear in the September 13 online edition of the journal Genes
& Development.
The work lays the foundation for a new approach to protecting
healthy tissue using small molecules to reduce p53 protein levels
in cells following damage caused by a wide range of factors,
including the radiation and chemotherapy used to treat cancer or
accidental exposure to dangerous chemicals or radiation, said
Michael Kastan, M.D., Ph.D., director of the St. Jude Comprehensive
Cancer Center and the paper’s senior author. The same approach
might also help ease the tissue damage that occurs as blood flow
and oxygen are restored following a heart attack or stroke.
“We are excited about this because we now theoretically have a
way of blunting p53 induction in settings where it is detrimental,”
he said.
The work builds on previous research from Kastan’s laboratory
into the mechanics of how p53 protein increases in response to
cellular stress and DNA damage. Jing Chen, Ph.D., a postdoctoral
fellow in Kastan’s laboratory, is first author of the study.
The jump in p53 protein production was wide
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