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Landmark study opens door to new cancer, aging treatments
Date:8/31/2008

ctive in cells that multiply frequently, such as embryonic stem cells, but is switched off almost entirely in normal adult cells to prevent the dangers of runaway cell proliferation.

Cancer cells, however, often regain the ability to activate telomerase, which has been implicated in 90 percent of human tumors. The enzyme permits cells to replicate indefinitely and achieve the cellular "immortality" that is the hallmark of cancer. Deactivating telomerase would stop tumor growth.

In addition to its role in cancer, telomerase holds significant implications for the development of therapies to combat aging and other age-related diseases. Finding ways to activate telomerase under controlled conditions and allow some cells to begin dividing again could result in healthier, younger-looking tissue that lives longer.

An elusive enzyme

Telomerase is a complex structure made up of multiple protein domains and a stretch of RNA, which contains the template the enzyme uses to synthesize telomeres.

Last year, Skordalakes and his team solved the structure of a key segment of the moleculethe so-called TRBD domain, where RNA binding occurs. However, the complexity of telomerase has proved a roadblock to determining the enzyme's overall architecturea goal pursued by researchers worldwide for more than 15 years.

To perform the necessary studies, scientists first must gather large quantities of the enzyme in a specific conformation. Because the complex structure of telomerase most likely allows it to change configuration, that process has been challenging, Skordalakes says.

To find sufficient quantities of the enzyme for the study, Skordalakes and his team looked beyond commonly relied-on sources such as humans and yeast. By screening a wide variety of organisms, including protozoa and insects, they discovered that a gene from the red flour beetle could produce telomerase in copious amounts, and a stable form.


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Contact: Abbey J. Porter
aporter@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

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