Media Contact: Sue Pondrom
Degradation and Growth are Topics of
Two Separate Articles in Science
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
"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.
On the Way to Becoming an
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."