Structural highlights
Function[PIN1_HUMAN] Essential PPIase that regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Displays a preference for an acidic residue N-terminal to the isomerized proline bond. Catalyzes pSer/Thr-Pro cis/trans isomerizations. Down-regulates kinase activity of BTK. Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation.[1] [2] [3] Publication Abstract from PubMedThe most active anticancer component in green tea is epigallocatechin-3-gallate (EGCG). The human peptidyl prolyl cis/trans isomerase (Pin1) plays a critical role in oncogenic signaling. Herein, we report the X-ray crystal structure of the Pin1/EGCG complex resolved at 1.9 A resolution. Notably, the structure revealed the presence of EGCG in both the WW and PPIase domains of Pin1. The direct binding of EGCG with Pin1 was confirmed and the interaction inhibited Pin1 PPlase activity. In addition, proliferation of cells expressing Pin1 was inhibited and tumor growth in a xenograft mouse model was suppressed. The binding of EGCG with Arg17 in the WW domain prevented the binding of c-Jun, a well-known Pin1 substrate. EGCG treatment corresponded with a decreased abundance of cyclin D1 and diminution of TPA-induced AP-1 or NFkappaB promoter activity in cells expressing Pin1. Overall, these results showed that EGCG directly suppresses the tumor promoting effect of Pin1. Epigallocatechin-gallate suppresses tumorigenesis by directly targeting Pin1.,Urusova D, Shim J, Kim DJ, Jung SK, Zykova T, Carper A, Bode AM, Dong Z Cancer Prev Res (Phila). 2011 Jul 12. PMID:21750208[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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