This collaborative work with Drs. Applla's groups involves the design of inhibitors of Wip1, which is the wild-type p53-induced phosphatase. It dephosphorylates a threonine residue on p38 MAPK and mediates a negative feedback loop in p38 MAPK-p53 signaling pathway. Wip1 is over-expressed in several human tumor types and acts as an oncogene. Thus, inhibition of Wip1 has become a strategy for treating certain type of cancer. Dr. Appella's group have designed a cyclized seven-residue peptide that can inhibit Wip1. We have determined the structure of this peptide using multi-dimensional NMR. The structure of the peptide will provide a lead for further design of small molecule drugs.
