Identification and characterization of a novel and functional murine Pin1 isoform.

  title={Identification and characterization of a novel and functional murine Pin1 isoform.},
  author={Jeff X. Zhu and Eleanor Dagostino and Paul A. Rejto and Barbara Mroczkowski and Brion W. Murray},
  journal={Biochemical and biophysical research communications},
  volume={359 3},
Pin1, a phosphorylation-dependent peptidyl-prolyl cis/trans isomerase (PPIase), regulates the activity of a number of cell cycle regulators, transcription factors, and microtubule-associated tau. Aberrant expression of Pin1 is implicated in carcinogenesis and neurodegenerative diseases. Yet, there are discrepancies regarding its biological significance in different organisms. Pin1 was essential in HeLa cells, while Pin1-deficient mice showed no lethal phenotypes. We here identified a novel… Expand
Oncogenic Hijacking of the PIN1 Signaling Network
This review focuses on molecular mechanisms and cellular processes like proliferation, metabolism, and stem cell fate, that are regulated by PIN1 in physiological conditions, discussing how these are subverted in and hijacked by cancer cells. Expand
The Caenorhabditis elegans parvulin gene subfamily and their expression under cold or heat stress along with the fkb subfamily.
This work presents a first attempt to characterize the Caenorhabditis elegans parvulins and may present an interesting starting point for further experimentation concerning their role, along with the FKBP subfamily, in nematode physiology and their possible use as antiparasitic targets. Expand
The prolyl isomerase PIN1: a pivotal new twist in phosphorylation signalling and disease
The prolyl isomerase PIN1 has been identified as a regulator of phosphorylation signalling that catalyses the conversion of specific phosphorylated motifs between the two completely distinct conformations in a subset of proteins. Expand
Pinning down signaling in the immune system: the role of the peptidyl-prolyl isomerase Pin1 in immune cell function.
How Pin1 modulates cytokine expression by activated T cells and eosinophils and participates in T-cell and eOSinophil apoptotic decisions both in vitro and in vivo is described. Expand
Peptidyl-prolyl isomerase activity in chloroplast thylakoid lumen is a dispensable function of immunophilins in Arabidopsis thaliana.
It is concluded that cellular functions of immunophilins in the thylakoid lumen of chloroplasts are not related to their PPIase capacity and should be investigated beyond this enzymatic activity. Expand
Mitotic Regulation of SEPT9 Protein by Cyclin-dependent Kinase 1 (Cdk1) and Pin1 Protein Is Important for the Completion of Cytokinesis*
It is demonstrated that cyclin-dependent kinase 1 phosphorylates septin 9 (SEPT9) upon mitotic entry, and this phosphorylation controls association with the proline isomerase, Pin1, which suggests that SEPT9 plays multiple roles in abscission, one of which is regulated by the action of Cdk1 and Pin1. Expand
Function and Regulation of Septins During Mammalian Cell Division
Septins are a family of GTP-binding proteins implicated in mammalian cell division. Since these proteins form heterologous complexes and filaments in interphase cells, it has been assumed thatExpand
Human chromosome segregation involves multi-layered regulation of separase by the peptidyl-prolyl-isomerase Pin1.
It is shown that securin-independent inhibition of separase by Cdk1-cyclin B1 in early mitosis requires the phosphorylation-specific peptidyl-prolyl cis/trans isomerase Pin1, and isomerization of previously secur in-bound separase at the metaphase-to-anaphase transition renders it resistant to re-inhibition by residual securInhibition. Expand
Structure-based design of novel human Pin1 inhibitors (I).
Without a viable lead from internal screenings, a series of novel Pin1 inhibitors were designed by interrogating and exploring a protein crystal structure of Pin1 by integrating SBDD and parallel chemistry approaches to create a more attractive lead series. Expand
ASPMF: a new approach for identifying alternative splicing isoforms using peptide mass fingerprinting.
A new method is developed that effectively distinguishes a true isoform among multiple isoforms in a gene, and 94% of true isoforms were identified by the scoring algorithm. Expand


Loss of Pin1 function in the mouse causes phenotypes resembling cyclin D1-null phenotypes
  • Y. Liou, A. Ryo, +6 authors K. Lu
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2002
The results indicate that Pin1 positively regulates cyclin D1 function at the transcriptional level, and also through posttranslational stabilization, which together explain why Pin1 loss-of-function phenotypes in the mouse resemble cyclIn D1-null phenotypes. Expand
Phosphorylation-dependent proline isomerization catalyzed by Pin1 is essential for tumor cell survival and entry into mitosis.
  • J. Rippmann, S. Hobbie, +7 authors A. Schnapp
  • Biology, Medicine
  • Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
  • 2000
The results of all of the three lines of investigation show that the catalytic activity of Pin1 is essential for tumor cell survival and entry into mitosis. Expand
Comparative analysis of enzyme activities and mRNA levels of peptidyl prolyl cis/trans isomerases in various organs of wild type and Pin1 −/− mice
The results show that high PPIase activities of Pin1 are found in organs that have the tendency to develop Pin1 knockout phenotypes and provide the first time an enzymological basis for these observations. Expand
Prevalent overexpression of prolyl isomerase Pin1 in human cancers.
Results indicate that Pin1 overexpression is a prevalent and specific event in human cancers and that inhibition of Pin1 can suppress transformed phenotypes and inhibit tumor cell growth, which may have important implications for the pathogenesis, diagnosis, and treatment of human cancers. Expand
A human peptidyl–prolyl isomerase essential for regulation of mitosis
Pinl is an essential PPIase that regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity, and is structurally and functionally related to Essl/Ptfl, an essential protein in budding yeast. Expand
The mitotic peptidyl‐prolyl isomerase, Pin1, interacts with Cdc25 and Plx1
It is demonstrated that depletion of Pin1‐binding proteins from Xenopus egg extracts results in hyperphosphorylation and inactivation of the key mitotic regulator, Cdc2/cyclin B, and biochemically it is shown that Pin1 may modulate cell cycle control through interaction with Cdc25 and its activator, Plx1. Expand
Role of Pin1 in the Regulation of p53 Stability and p21 Transactivation, and Cell Cycle Checkpoints in Response to DNA Damage*
A new role is demonstrated in regulating p53 function during DNA damage that depended on the WW domain in Pin1 and Ser33/46-Pro motifs in p53, and Pin1 regulates the stability of p53 and its transcriptional activity toward the p21 promoter. Expand
Pin1 allows for differential Tau dephosphorylation in neuronal cells
Data indicate that Pin1 has key function(s) in neuron and is at least involved in the regulation of Tau phosphorylation at relevant sites, and Pin1 dysfunction, unlikely by nuclear depletion, may have critical consequences on Tau pathological aggregation and neuronal death. Expand
The Loss of PIN1 Deregulates Cyclin E and Sensitizes Mouse Embryo Fibroblasts to Genomic Instability*
It is shown that Pin1 regulates the turnover of cyclin E in mouse embryo fibroblasts and predisposes Pin1 null mouse embryos to undergo more rapid genomic instability when immortalized by conditional inactivation of p53 and sensitizes these cells to more aggressive Ras-dependent transformation and tumorigenesis. Expand
PIN1 Is an E2F Target Gene Essential for Neu/Ras-Induced Transformation of Mammary Epithelial Cells
It is demonstrated that Pin1 expression is mediated by the transcription factor E2F and enhanced by c-Neu and Ha-Ras via E2f and not only confers transforming properties on mammary epithelial cells but also enhances the transformed phenotypes of Neu/Ras-transformed mammary intestinal cells. Expand