Did You Ever Wonder . . ?
Kunxin Luo  

A molecular terminator

When Berkeley Lab cell biologist Kunxin Luo and her research group discovered the mechanism by which Sno, a tumor-promoting family of proteins, interacted with Smad, a tumor-suppressing family of proteins, they found that an accumulation of Smad in the nucleus resulted in the degradation of Sno. They wanted to know how Smad was accomplishing this. The answer was a hitchhiker known as the anaphase promoting complex (APC) of proteins.

APC is well known by biologists as the molecule that breaks apart the connections between daughter cells during cell division. No one had ever reported a role for APC in the development of cancer.

Luo and her group showed that as Smad proteins enter the cell nucleus they pick up APC proteins and bring them along to chop up the Sno. The Sno proteins contain a region called a "destruction box" that has a similar molecular motif to the molecular regions that the APC targets during cell division.

More about the role of APC in cancer

Tagged Smads

Berkeley Lab cell biologist Kunxin Luo and her colleagues were able to identify the roles played by the Ski and Sno proteins in cancer development by working with liver cancer cells of a type known as Hep3B cells. They began this research to identify proteins in the cell nucleus that interact with Smad proteins, which earlier work had identified as carriers of the TGF-ß signal - a cell signal that controls many important cell functions including growth and differentiation.

To conduct their search, they engineered a Smad protein to host a special molecular "tag" that would be recognized by an antibody. Tagged Smad proteins could then be introduced into cells and subsequently harvested using the antibody. Caught up in the harvest would be any other type of protein that might be attached to the tagged Smads.

 


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Ernest Orlando Lawrence Berkeley National Laboratory