Puny Pin1 > –/– Mice

Abstract

Pin1 is a prolyl isomerase that regulates the activity of specific proteins by promoting the isomerization of the phosphorylated Ser-Pro or phosphorylated Thr-Pro bond. Liou et al . analyzed the phenotypes of the Pin1 –/– mice and found that adult animals exhibited several characteristics of cell proliferative defects: decreased body weight, testicular and retinal atrophy, and impaired mammary gland development during pregnancy. Because these phenotypes are also characteristic of mice deficient in cyclin D1, Liou et al . examined cyclin D1 in the Pin1 –/– mice and found that cyclin D1 protein levels were reduced in several tissues that are normally proliferating, including the Pin1 –/– -affected tissues. Analysis of cyclin D1 in Pin1 –/– mouse embryonic fibroblasts (MEFs) showed that in addition to decreasing cyclin D1 transcription, loss of Pin1 also resulted in decreased stability of cyclin D1 and redistribution of cyclin D1 to the cytoplasm compared with the nuclear localization typical of wild-type MEFs. The effects of Pin1 and binding of Pin1 to cyclin D in glutathione S -transferase pull-down experiments were dependent on the presence of a Thr that can be phosphorylated and is located in a Pin1 consensus motif. Thus, Pin1 appears to regulate cyclin D1 at both the transcriptional and posttranscriptional level to control cell proliferation. Y.-C. Liou, A. Ryo, H.-K. Huang, P.-J. Lu, R. Bronson, F. Fujimore, T. Uchida, T. Hunter, K. P. Lu, Loss of Pin1 function in the mouse causes phenotypes resembling cyclin D1-null phenotypes. Proc. Natl. Acad. Sci. U.S.A. 99 , 1335-1340 (2002). [Abstract] [Full Text]