“Our paper defines a new sequence motif that underlies a protealytic activity.”

I feel our paper accomplished two things which have a broad appeal to the field. First, it discovered the molecular basis for a previously ill-defined activity, allowing us to directly test the extent to which this activity is contributing to cellular regulation. Second, in discovering this new molecular basis, we have identified an amino acid motif (which we call the JAMM motif—for the "Jab1/MPN domain metalloenzyme") which represents a new family of enzymes. Given that this motif is found in numerous cellular proteins, including a subunit of the 26S Proteasome, this discovery gives scientists the ability to test what role these new enzymes play in their particular pathway.

Yes. With the discovery of the JAMM motif, one is able to investigate the numerous proteins which contain this motif through point mutations which abolish activity, thus investigating the extent to which the JAMM activity contributes to the overall pathway the protein is in.

Our paper defines a new sequence motif that underlies a protealytic activity. In doing so, we have discovered a whole new family of enzymes that are found in numerous cellular processes. For example, one member of this family is found within the 26S Proteasome. Given the 26S Proteasome contributes to the bulk of cellular proteolysis, scientists can knock out this function to not only analyze 26S Proteasome substrates, but medical researchers can also utilize this knowledge in attempts to treat some diseases.

Serendipitously. A former graduate student in the lab, Svetlana Lyapina, was investigating the ubiquitin ligase complex SCF when she found CSN to be associated with SCF. Further research confirmed that CSN regulates SCF through neddylation, culminating in these recent findings.

Greg A. Cope
Dept. of Biology - Biochemistry Option
California Institute of Technology
R. Deshaies Lab
Pasadena, CA, USA