A large number of oncoproteins and tumor suppressors are directly regulated by proline-directed phosphorylation or trigger signalling pathways involving such phosphorylation, but how to coordinate these phosphorylation events was unclear. Our lab is the first one to show that Pin1 is overexpressed in most human cancers and correlated with poor clinical outcome and Pin1 overexpression promotes cancer and cancer stem cells by acting on multiple well-known oncogenic pathways, whereas Pin1 gene knockout or knockdown prevents tumorigenesis by multiple oncogenes or tumor suppressors in vitro and in vivo (EMBO J 2001, 2004; NCB 2001; PNAS, 2002; Mol Cell 2003). Pin1 is now shown to activate over 70 oncoproteins and inactivate ~30 tumor suppressors.
Dr. Lu Laboratory and Dr. Zhou Laboratory, Western University, 1400 Western Road, SDRI Room 107, London, Ontario N6G 2V4, Canada. The co-crystal structures of Pin1 and its inhibitors are generated by Shaunik Sharma using Pymol.
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