Biochemical "On/Off" Switch Discovered

PASADENA, Ca.— Proteins are the cell's arbiters. In a complex and still largely mysterious cascade of events, proteins tell a cell when to divide and grow—and when to die. To properly control cell behavior, proteins need to be turned on when they are needed, and turned off when they are not. Now a California Institute of Technology biologist and his colleagues have shed important new light on how this takes place in animals and plants.

In a paper published in the May 18 issue of the journal Science, biologist Raymond Deshaies and his graduate students show that an assemblage of proteins known as CSN may serve as a kind of biochemical on/off switch for other proteins.

In plants, research done in the laboratory of Deshaies's collaborator, Xing-Wang Deng of Yale University, has shown that CSN prevents photomorphogenesis (roughly, the growth of plants controlled by light) when light is absent. CSN is widely distributed in animals as well, but until now no one knew what any of its functions were. Now Deshaies's research shows that CSN may be linked to a recently discovered protein modification known as "neddylation," the physical attachment of a small protein, called NEDD8, to another protein. Neddylation is thought to alter the functioning of whatever protein NEDD8 attaches to. For example, when it attaches to the enzyme SCF (previously discovered by the Deshaies's team), SCF activity increases dramatically. Although the enzymes that attach NEDD8 to proteins like SCF were already known, the enzymes that remove it were not.

Deshaies's team discovered that CSN removes the NEDD8 that is attached to SCF. Based on this finding, they conclude that CSN controls the on-and-off switching of proteins. For example, when NEDD8 is not removed from its partners in plant cells, the plant doesn't respond normally to hormones that control its development.

Many different physiological roles have been proposed for CSN, including roles in the synthesis of new proteins, control of cell division, and control of inflammation. The Deshaies team's finding that CSN acts by removing NEDD8 from other proteins suggests that NEDD8, in turn, is likely to serve as a linchpin in these processes.

Deshaies and his laboratory colleagues are interested in the regulation of cell division, and in identifying the specific functions of various proteins within a cell that participate in this process. The proper regulation of cell division is critical for the normal development of organisms. In animals, aberrations in cell division can have profound consequences; unchecked cell division, for example, can lead to cancer.