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.
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.