A human peptidyl-prolyl isomerase essential for regulation of mitosis.
The NIMA kinase is essential for progression through mitosis in Aspergillus nidulans, and there is evidence for a similar pathway in other eukaryotic cells. Here we describe the human protein Pin1, a peptidyl-prolyl cis/trans isomerase (PPIase) that interacts with NIMA. PPIases are important in protein folding, assembly and/or transport, but none has so far been shown to be required for cell viability. Pin1 is nuclear PPIase containing a WW protein interaction domain, and is structurally and functionally related to Ess1/Ptf1, an essential protein in budding yeast. PPIase activity is necessary for Ess1/Pin1 function in yeast. Depletion of Pin1/Ess1 from yeast or HeLa cells induces mitotic arrest, whereas HeLa cells overexpressing Pin1 arrest in the G2 phase of the cell cycle. Pin1 is thus an essential PPIase that regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity.
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Molecular Biology and Virology Laboratory, The Salk Institute, La Jolla, California 92037, USA.
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Hunter
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D000591:Amino Acid Isomerases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D001230:Aspergillus / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D005656:Fungal Proteins / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D000072380:NIMA-Related Kinase 1; D000072379:NIMA-Related Kinases; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D019696:Peptidylprolyl Isomerase; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C000606914:NEK1 protein, human; D000072380:NIMA-Related Kinase 1; D000072379:NIMA-Related Kinases; C442331:NIMA-related kinase 6; D017346:Protein Serine-Threonine Kinases; D000591:Amino Acid Isomerases; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase