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

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概要

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• 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' 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's 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.

• 東北大学の論文

著者

• Tatara Yota

  Molecular Enzymology Molecular Cellular Biology Agricultural Science Tohoku University

• AKIYAMA Hirotada

  Molecular Enzymology, Molecular Cellular Biology, Agricultural Science, Tohoku University

• UCHIDA Takafumi

  Molecular Enzymology, Molecular Cellular Biology, Agricultural Science, Tohoku University

• Uchida Takafumi

  Lab. Of Enzymology Graduate School Of Agricultural Sci. Tohoku Univ.

• Uchida Takafumi

  Molecular Enrymology Department Of Molecular Cell Science Graduate School Of Agricultural Science To

• Akiyama Hirotada

  Molecular Enzymology Molecular Cellular Biology Agricultural Science Tohoku University

関連論文

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