Our primary research interest is to elucidate the role and regulation of telomere maintenance in aging and age-related disease such as cancer. We have previously shown that Pin2/TRF1 is a dual function protein important for regulating telomere maintenance and cell cycle progression. Furthermore, by screening for new Pin2//TRF1-interacting proteins, we have discovered a number of new Pin2/TRF1-interacting proteins, including four novel genes called PinX1-4, and shown that these proteins play a major role in telomere maintenance and human disease. More notably, PinX1 is a potent telomerase inhibitor and a major tumor suppressor located at chromosome 8p23, a frequent loss of heterozygosity region in a number of human cancers. Further studies on these novel proteins may provide novel insight into telomere regulation and its role in aging and age-related disease.
Zhou, X. Z., Kops, O., Werner, A., Shen, M., Lu, P. J. Stoller, G., Küllertz, G., Fisher, G. and Lu, K. P. 2000, Regulation of Protein Dephosphorylation by Phosphorylation-Specific Prolyl Isomerization. Mol. Cell 6: 873-883.
Zhou, X. Z. and Lu, K. P. 2001, The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor. Cell 107: 347-359.
Lee, T. H., Perrem, K., Harper, W., Lu, K. P. and Zhou, X. Z. 2006, The F-box protein Fbx4 targets Pin2/TRF1 for ubiquitin-mediated degradation and regulates telomere maintenance. J. Biol. Chem. 281:759-768.
Lu, K. P. and Zhou, X. Z., 2007, The prolyl isomerase Pin1: A pivotal new twist in phosphorylation signalling and disease. Nature Reviews Mol. Cell. Biol. 8: 904-916.
Lee, T. H., Lim, J., Tun-Kyi, A., Finn, G., Shi, R., Balastik, M., Pastorino, L., Wulf, Zhou, X. Z.* and Lu, K. P.* (*share the corresponding authorship) 2008, Essential role of the phosphorylation specific isomerase Pin1 in regulating TRF1 protein stability, telomere maintenance and aging. Nature Cell Biol (accepted).
