Researchers Unmask Proteins In Telomerase, A Substance That Enables
Cancer
ScienceDaily (Mar. 21, 2008) — One of the more intriguing workhorses
of the cell, a protein conglomerate called telomerase, has in its
short history been implicated in some critical areas of medicine
including cancer, aging and keeping stem cells healthy. With such a
resume, telomerase has been the subject of avid interest by basic
scientists and pharmaceutical companies alike, so you'd think at the
very least people would know what it is.
But researchers have been frustrated in their attempts to find the
proteins that make up this complex. They know that it's a behemoth of
an enzyme and is made up of more than just the two components they've
gotten their hands on in the past. They also know what it does: it
maintains the cell's genetic material in fetal cells, normal adult
stem cells and in cancer cells.
What they don't know is what other proteins make up the massive
telomerase complex. Until now, that is.
Researchers at Stanford University School of Medicine have identified
two new proteins that make up the telomerase complex and have a lead
on several more. This is the first significant step toward
understanding the makeup of telomerase since 1999. The discovery of
these two proteins provides new targets for cancer treatments, the
researchers said.
"It's so surprising that we are discovering new components of this
enzyme almost ten years after it was discovered," said Steven
Artandi, MD, PhD, assistant professor of medicine and senior author
of the study. The work will be published in the March 21 issue of
Cell.
Telomerase is best known for its role in maintaining the cell's
genetic material, the chromosomes. Every time a person's cell
divides, it makes a second copy of the 46 chromosomes, then sends one
copy to each of the two resulting cells. As that copying process
proceeds, each replication snips a bit off the protective tips of the
chromosomes, called telomeres. Those ever-shortening chromosomes are
one reason cells age. After a lifetime of cells dividing, the
telomeres dwindle down to a length that eventually triggers the cell
to stop replicating altogether or die.
Cancerous cells overcome that lifespan limitation by making
telomerase, which repairs those snipped chromosome ends. Without
shortening, the cells can divide forever. Telomerase is normally
active in fetal cells, then shortly after birth it is turned off in
all cells except normal tissue stem cells and some immune cells.
Since telomerase's discovery in cancerous cells in 1994, the idea has
been that if a drug could block telomerase, chromosomes in those
cancerous cells would eventually grow shorter and the cells would age
and die just like any other cell in the body. But without knowing
what proteins make up telomerase it's hard to design a drug to block
it.
In the study, Artandi and first author Andrew Veneicher, an MD/PhD
student, describe two protein components of telomerase. They also
show that disabling one of the proteins brings telomerase to a
grinding halt. Although the work was done in cells in a lab dish, the
findings suggest that a drug blocking that protein may be a useful
tool against cancer.
Artandi said one problem with studying telomerase is that it's
available in such small quantities. Growing huge vats of cancer cells
in the lab still only results in miniscule amounts of protein. Until
recently, no technology was sensitive enough to analyze proteins at
such minute levels.
"Many technical advances feed into our ability to make this
discovery," Artandi said.
Artandi and his colleagues at the National Cancer Institute and
Washington University School of Medicine took advantage of new
technologies to get around the quantity problem. They chopped the
massive telomerase complex into tiny protein pieces, then sent those
pieces through a sensitive device that detected the pieces and
compared the protein sequence to a genetic database that could match
the snippet to a particular gene.
With the gene in hand, the researchers could find the protein made by
that gene. They also used genetic trickery to disable one of the
proteins, which prevented the telomerase from working. Artandi said
the next step is to find small molecules that can block that newly
discovered protein in cancerous cells. He's also trying to identify a
handful of additional proteins that seem to be part of the telomerase
complex.
The work was funded by the National Cancer Institute, the National
Institutes of Health, the American Federation of Aging
Research/Pfizer, and the Medical Scientists Training Program Grant.
Adapted from materials provided by Stanford University Medical
Center, via EurekAlert!, a service of AAAS.
Need to cite this story in your essay, paper, or report? Use one of
the following formats:
APA
MLA Stanford University Medical Center (2008, March 21). Researchers
Unmask Proteins In Telomerase, A Substance That Enables Cancer.
ScienceDaily. Retrieved March 28, 2008, from
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