New discovery builds better target for anticancer drug development

CHICAGO, Jan. 31 (Xinhua) -- University of Michigan (UM) researchers have identified a region on a protein called TPP1 that binds an enzyme called telomerase.

This could provide a target for anticancer drugs development, as about 90 percent of cancers, irrespective of the type, kind, stage, tissue or organ, actually switch on telomerase, the UM press release quoted UM researcher Jayakrishnan Nandakumar, lead author of the study, as saying on Tuesday.

Most normal cells in human body don't divide and so do not have telomerase, but cancerous cells often activate telomerase, causing the cells to divide ceaselessly and booting cancer growth.

In order to find how telomerase travels to the end of chromosomes, UM researchers resort to the assistance of a protein called TPP1, and discovered a region called TEL patch on TPP1 that allows the telomerase to bind to chromosome ends.

Previously, researchers thought there was only one protein region that binds telomerase to chromosome ends. Now, they have discovered a second region on TPP1 that assists in binding telomerase to chromosomes, and named the region NOB after its location, the N-terminus of the OB domain of TPP1.

The two regions composed of amino acids work together to provide a full platform for telomerase to engage chromosome ends.

To test the importance of the newly discovered region, the team swapped the NOB section of the mouse TPP1 protein with the human NOB region. Once the NOB sections were replaced, mouse TPP1 began stimulating human telomerase, showing that NOB was crucial in the binding of telomerase.

The discovery could help inform years of research that combines anticancer drugs with drugs that shut down telomerase activity.

"It's a big deal because telomerase is a great anticancer target," Nandakumar said. "It's not present in every single cell in the body, and so if you stop telomerase somehow, cancer cells can't re-elongate their chromosomes, and they would ultimately die."

Having discovered where telomerase binds TPP1, UM researchers now hope to determine where TPP1 binds telomerase. Enditem