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Molecular Biologist Discusses Role of Autophagy
Autophagy, the process of self-digestion of cell components through the action of enzymes within a cell, plays a vital role in cell maintenance and development, but in recent years has also been linked to a growing number of human diseases, including neurodegenerative conditions, cardiovascular disease and breast cancer.
In the Dec. 1, 2000 issue of the journal Science, UCSD professor of cellular and molecular medicine and Howard Hughes Medical Institute investigator Scott D. Emr, Ph.D., reviews recent findings regarding autophagy and advances made in identifying its molecular components.
Along with co-author Daniel J. Klionsky from the University of Michigan, Emr notes that autophagy, the breakdown and recycling of cellular material, is seen in yeast, plants and animals. Although first identified more than 20 years ago, scientific interest in autophagy was fairly modest until the identification about five years ago of several of the molecular components underlying this important process. Since then, some 30 genes have been identified as part of the autophagy pathway. Within the past two years, researchers have identified a link between decreased levels of one of these genes, called beclin 1, and breast cancer.
“There are many lines of evidence that connect autophagy to human disease,” Emr says. Lower levels of autophagy genes have been linked to cancer and heart disease, while elevated expression of autophagy is associated with neurodegenerative diseases such as Parkinson’s.
In the Science review, Emr and Klionsky note that several questions remain for researchers, including the mechanism by which cells sense the need for autophagy and the specific roles of genes within the autophagy pathway.
In the Nov. 10, 2000 issue of the journal Science, UCSD School of Medicine researcher Kathleen Scully, Ph.D. and her team reported their study of how a transcription factor (or molecular master switch) called Pit-1 works to turn specific target genes off and on in different hormone-producing cells of the pituitary gland.
Their findings may help explain how a group of similar cells become different from one another during the development of organs and other tissues that are made up of many different types of cells.
The UCSD researchers studied three different cells in the pituitary gland that make three different types of hormones – growth hormone, prolactin and thyrotropin. Although each cell includes the genes for all three hormones in its chromosomes, Pit-1 “turns on” just one so that a given cell produces a single hormone.
In studies with mice, the researchers found that Pit-1 activates the right hormone gene in each cell type, and represses the others, and that this occurs because Pit-1 binds to each gene with a different shape due to a small variation in the DNA sequences of the genes.
In an accompanying commentary in the Nov. 10 issue of Science, editor Jean Marx notes that “the finding supports the idea that the sequences that bind transcription factors are more than just docking sites…structural change can in turn influence which other proteins bind to the transcription factor on the regulatory site – and ultimately, whether genes are turned on or off.”
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