Novel Functions of Prolyl Isomerase Pin1(Recent Topics of the Agricultunal Biological Science in Tohoku University)

We have studied the novel functions of peptidyl prolyl cis/trans isomerase Pin1 that specifically binds the phosphorylated Ser/Thr-Pro protein motifs and catalyzes the cis/trans isomerization of the peptide bond. Accumulating studies have revealed that Pin1 isomerase activity is regulated by its post-translational modifications, including phosphorylation and oxidation. Various transcription factors and regulators have been identified as substrates for Pin1. It enhances AP-l activity via isomerization of both c-Jun and c-Fos for cellular proliferation and stabilizes the oncosuppressors p53 and p73 against DNA damage at the checkpoint. We demonstrated the association between the intracellular form of Notchl (NIC) and Pin1 by analyzing Pin1/p53 double knockout mice. Pin1 also regulates the posttranscriptional level of some cytokines, associated with asthma, that possess 3\u27 untranslated region AU-rich elements (ARE) via interaction with AUF-1, the nucleoprotein in the ARE-binding complex. Pin1 has been identified as the molecular partner of tau and amyloid precursor protein (APP), the key factors of Alzheimer\u27s disease (AD). It interacts with the phosphorylated Thr-231 of tau and regulates its activity to bind microtubules. It further interacts with the phosphorylated Thr-668 of APP and affects its metabolism. Thus, Pin1 is probably involved in the pathogenesis of human pathologies, including cancer, asthma and AD, presenting an attractive target for future therapeutical drugs

Prolyl Isomerase Pin1 Protects Mice from Endotoxin Shock

Prolyl isomerase Pin1 may be involved in innate immunity against microbial infection, but the mechanism how Pin1 controls the innate immunity is poorly understood.Injection of lipopolysaccharide (LPS) into the mice induces inflammatory pulmonary disorder and sometimes the serious damages lead to death. Comparing to the wild-type (WT) mice, the Pin1⁻/⁻ mice showed more serious damages in lung and the lower survival rate after the LPS injection. We compared the levels of typical inflammatory cytokines. Pin1⁻/⁻ mice overreacted to the LPS injection to produce inflammatory cytokines, especially IL-6 more than WT mice. We showed that Pin1 binds phosphorylated PU.1 and they localize together in a nucleus. These results suggest that Pin1 controls the transcriptional activity of PU.1 and suppresses overreaction of macrophage that causes serious damages in lung.Pin1 may protect the mice from serious inflammation by LPS injection by attenuating the increase of IL-6 transcription of the mouse macrophages

Prolyl Isomerase Pin1 Directly Regulates Calcium/Calmodulin-Dependent Protein Kinase II Activity in Mouse Brains

Calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the brain and functions as a mediator of calcium signaling. We found that the relative activity of CaMKII was significantly lower in the WT mouse brains than in the Pin1-/- mouse brains. Pin1 binds to phosphorylated CaMKII and weakens its activity. For this reason, the phosphorylation level of tau in the presence of Pin1 is lower than that in the absence of Pin1, and microtubule polymerization is not downregulated by CaMKII when Pin1 is present. These results suggest a novel mechanism of action of Pin1 to prevent neurodegeneration

Surgical Treatment for Skeletal Metastases From Soft Tissue Sarcomas: Experience With 23 Lesions in 20 Patients

Purpose. This paper reports the procedures and the clinical results of a series of surgical treatments for skeletal metastases from soft tissue sarcomas

Geochemical and radiogenic isotopic signatures of granitic rocks in Chanthaburi and Chachoengsao provinces, southeastern Thailand : Implications for origin and evolution

The Chanthaburi, Pliew, Klathing, Khao Cha Mao, and Khao Hin Son granitic bodies in Chanthaburi and Chachoengsao provinces in southeastern Thailand, which are located on the southwestern side of the Mae Ping Fault and eastern side of the Klaeng Fault, were investigated. In this study, magnetic susceptibility measurements, whole-rock chemical composition and Nd-Sr isotope analyses, and zircon U-Pb dating were conducted on these granitic bodies. The surveyed granitic rocks are classified as I- to A-type granites, are of the ilmenite series, and show clearly negative Eu anomalies, which suggest they formed under reducing conditions. Nd-Sr isotope ratios indicate continental crust material involvement in the formation of these granite bodies. The magnetic and geochemical signatures are similar to those of granite bodies in southwestern Cambodia. The study area is thus considered an extensional area of southwestern Cambodia, corresponding to the Sukhothai Zone (the Chanthaburi-Kampong Chhnang Zone). Zircon U-Pb dating yields ages of 208–214 Ma (the Late Triassic) for granite bodies except for the Khao Cha Mao granitic body, which dates to 55 Ma. The former age corresponds to the collision time of the Sibumasu and Indochina terranes, and the latter age is likely related to the collision time of the Indian and Eurasian continents