A Guide to PIN1 Function and Mutations Across Cancers

PIN1 is a member of a family of peptidylprolyl isomerases that bind phosphoproteins and catalyze the rapid cis–trans isomerization of proline peptidyl bonds, resulting in an alteration of protein structure, function, and stability. PIN1 is overexpressed in human cancers, suggesting it promotes tumorigenesis, but depending on the cellular context, it also acts as a tumor suppressor. Here, we review the role of PIN1 in cancer and the regulation of PIN1 expression, and catalog the single nucleotide polymorphisms, and mutations in PIN1 gene associated with cancer. In addition, we provide a 3D model of the protein to localize the mutated residues.

[1]  PIN1 Gene , 2020, Definitions.

[2]  V. Canzonieri,et al.  Liposomal delivery of a Pin1 inhibitor complexed with cyclodextrins as new therapy for high‐grade serous ovarian cancer , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[3]  H. Oki,et al.  Discovery of an Orally Bioavailable, Brain-Penetrating, in Vivo Active Phosphodiesterase 2A Inhibitor Lead Series for the Treatment of Cognitive Disorders. , 2017, Journal of medicinal chemistry.

[4]  A. Rosato,et al.  A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action , 2017, Nature Communications.

[5]  Mingming Jia,et al.  COSMIC: somatic cancer genetics at high-resolution , 2016, Nucleic Acids Res..

[6]  Xiaoguang Chen,et al.  Synthesis and Pin1 inhibitory activity of thiazole derivatives. , 2016, Bioorganic & medicinal chemistry.

[7]  A. Ryo,et al.  Discovery of novel selenium derivatives as Pin1 inhibitors by high-throughput screening. , 2016, Biochemical and biophysical research communications.

[8]  Xiao Zhen Zhou,et al.  The isomerase PIN1 controls numerous cancer-driving pathways and is a unique drug target , 2016, Nature Reviews Cancer.

[9]  Shan Li,et al.  PIN1 genetic polymorphisms and the susceptibility of HBV-related hepatocellular carcinoma in a Guangxi population , 2016, Tumor Biology.

[10]  Chandra Sekhar Pedamallu,et al.  Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas , 2016, Nature Genetics.

[11]  S. Gabriel,et al.  Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma , 2016, Cell reports.

[12]  Matteo Benelli,et al.  Divergent clonal evolution of castration resistant neuroendocrine prostate cancer , 2016, Nature Medicine.

[13]  Nam Huh,et al.  Exome sequencing of desmoplastic melanoma identifies recurrent NFKBIE promoter mutations and diverse activating mutations in the MAPK pathway , 2015, Nature Genetics.

[14]  S. Ariyan,et al.  Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas , 2015, Nature Genetics.

[15]  P. Pandolfi,et al.  Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer , 2015, Nature Medicine.

[16]  D. Butterfield,et al.  Pin1 cysteine-113 oxidation inhibits its catalytic activity and cellular function in Alzheimer's disease , 2015, Neurobiology of Disease.

[17]  Jessica Zucman-Rossi,et al.  Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets , 2015, Nature Genetics.

[18]  Steven J. M. Jones,et al.  Comprehensive genomic characterization of head and neck squamous cell carcinomas , 2015, Nature.

[19]  B. Arun,et al.  Cancers Associated with Brca1 and Brca2 Mutations Other than Breast and Ovarian Cancers Associated with Brca1 and Brca2 Mutations Other than Breast and Ovarian , 2022 .

[20]  Curtis R. Pickering,et al.  Mutational Landscape of Aggressive Cutaneous Squamous Cell Carcinoma , 2014, Clinical Cancer Research.

[21]  Kristian Cibulskis,et al.  RNF43 is frequently mutated in colorectal and endometrial cancers , 2014, Nature Genetics.

[22]  Genevieve D Paderes,et al.  Structure-based design of novel human Pin1 inhibitors (III): optimizing affinity beyond the phosphate recognition pocket. , 2014, Bioorganic & medicinal chemistry letters.

[23]  M. Hsiao,et al.  MicroRNA-296-5p (miR-296-5p) functions as a tumor suppressor in prostate cancer by directly targeting Pin1. , 2014, Biochimica et biophysica acta.

[24]  Steven J. M. Jones,et al.  Comprehensive molecular characterization of gastric adenocarcinoma , 2014, Nature.

[25]  J. Lieberman,et al.  Prolyl isomerase Pin1 acts downstream of miR200c to promote cancer stem-like cell traits in breast cancer. , 2014, Cancer research.

[26]  Liam O'Connor,et al.  Colorectal cancer cell lines are representative models of the main molecular subtypes of primary cancer. , 2014, Cancer research.

[27]  M. Toyota,et al.  Colorectal carcinomas with CpG island methylator phenotype 1 frequently contain mutations in chromatin regulators. , 2014, Gastroenterology.

[28]  Javed Siddiqui,et al.  Activating ESR1 mutations in hormone-resistant metastatic breast cancer , 2013, Nature Genetics.

[29]  Chi-Ying F. Huang,et al.  Pin1 acts as a negative regulator of the G2/M transition by interacting with the Aurora-A–Bora complex , 2013, Journal of Cell Science.

[30]  Zhihua Liu,et al.  Regulation of the MicroRNA 200b (miRNA-200b) by Transcriptional Regulators PEA3 and ELK-1 Protein Affects Expression of Pin1 Protein to Control Anoikis* , 2013, The Journal of Biological Chemistry.

[31]  Jeffrey W. Peng,et al.  Interdomain Interactions Support Interdomain Communication in Human Pin1 , 2013, Biochemistry.

[32]  Yun Lin,et al.  The rs2233678 Polymorphism in PIN1 Promoter Region Reduced Cancer Risk: A Meta-Analysis , 2013, PloS one.

[33]  H. Shih,et al.  SENP1 deSUMOylates and regulates Pin1 protein activity and cellular function. , 2013, Cancer research.

[34]  Z. Dong,et al.  Association between PIN1 promoter polymorphisms and risk of nasopharyngeal carcinoma , 2013, Molecular Biology Reports.

[35]  Colin J. Daniel,et al.  Pin1 Regulates the Dynamics of c-Myc DNA Binding To Facilitate Target Gene Regulation and Oncogenesis , 2013, Molecular and Cellular Biology.

[36]  Benjamin E. Gross,et al.  Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal , 2013, Science Signaling.

[37]  A. Giordano,et al.  The Prolyl Isomerase Pin1 Acts Synergistically with CDK2 to Regulate the Basal Activity of Estrogen Receptor α in Breast Cancer , 2013, PloS one.

[38]  Yifeng Zhou,et al.  Functional polymorphisms in PIN1 promoter and esophageal carcinoma susceptibility in Chinese population , 2013, Molecular Biology Reports.

[39]  A. Giordano,et al.  Dissecting Pin1 and phospho‐pRb regulation , 2013, Journal of cellular physiology.

[40]  A. Giordano,et al.  Androgen receptor serine 81 mediates Pin1 interaction and activity , 2012, Cell cycle.

[41]  Robert Gentleman,et al.  Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer , 2012, Nature Genetics.

[42]  A. Sivachenko,et al.  A Landscape of Driver Mutations in Melanoma , 2012, Cell.

[43]  Steven J. M. Jones,et al.  Comprehensive molecular characterization of human colon and rectal cancer , 2012, Nature.

[44]  K. Lu,et al.  Mixed-lineage kinase 3 phosphorylates prolyl-isomerase Pin1 to regulate its nuclear translocation and cellular function , 2012, Proceedings of the National Academy of Sciences.

[45]  Yong-Yeon Cho,et al.  TPA-induced cell transformation provokes a complex formation between Pin1 and 90 kDa ribosomal protein S6 kinase 2 , 2012, Molecular and Cellular Biochemistry.

[46]  Benjamin E. Gross,et al.  The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. , 2012, Cancer discovery.

[47]  A. Klein-Szanto,et al.  Retinoblastoma tumor-suppressor protein phosphorylation and inactivation depend on direct interaction with Pin1 , 2012, Cell Death and Differentiation.

[48]  C. V. Jongeneel,et al.  Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma , 2011, Nature Genetics.

[49]  Y. Liou,et al.  Prolyl isomerase Pin1 as a molecular switch to determine the fate of phosphoproteins. , 2011, Trends in biochemical sciences.

[50]  Jeffrey W. Peng,et al.  Stereospecific gating of functional motions in Pin1 , 2011, Proceedings of the National Academy of Sciences.

[51]  Jian Li,et al.  Temporal dissection of tumorigenesis in primary cancers. , 2011, Cancer discovery.

[52]  K. Lu,et al.  Peptidyl-prolyl cis–trans isomerase Pin1 in ageing, cancer and Alzheimer disease , 2011, Expert Reviews in Molecular Medicine.

[53]  S. Davis,et al.  Exome sequencing identifies GRIN2A as frequently mutated in melanoma , 2011, Nature Genetics.

[54]  T. Uchida,et al.  A dual inhibitor against prolyl isomerase Pin1 and cyclophilin discovered by a novel real-time fluorescence detection method. , 2011, Biochemical and biophysical research communications.

[55]  B. Davis,et al.  Discovery of cell-active phenyl-imidazole Pin1 inhibitors by structure-guided fragment evolution. , 2011, Bioorganic & medicinal chemistry letters.

[56]  Q. Wei,et al.  The functional promoter polymorphism (−842G>C) in the PIN1 gene is associated with decreased risk of breast cancer in non-Hispanic white women 55 years and younger , 2010, Breast Cancer Research and Treatment.

[57]  M. Karin,et al.  Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. , 2010, Cytokine & growth factor reviews.

[58]  B. Davis,et al.  Structure-guided design of alpha-amino acid-derived Pin1 inhibitors. , 2009, Bioorganic & medicinal chemistry letters.

[59]  Li-E. Wang,et al.  A novel functional variant (-842G>C) in the PIN1 promoter contributes to decreased risk of squamous cell carcinoma of the head and neck by diminishing the promoter activity. , 2009, Carcinogenesis.

[60]  Samantha Greasley,et al.  Structure-based design of novel human Pin1 inhibitors (I). , 2009, Bioorganic & medicinal chemistry letters.

[61]  Xi He,et al.  Wnt/beta-catenin signaling: components, mechanisms, and diseases. , 2009, Developmental cell.

[62]  X. Zhou,et al.  Peptidyl-prolyl cis/trans isomerase Pin1 is critical for the regulation of PKB/Akt stability and activation phosphorylation , 2009, Oncogene.

[63]  Pier Paolo Di Fiore,et al.  The prolyl-isomerase Pin1 is a Notch1 target that enhances Notch1 activation in cancer , 2009, Nature Cell Biology.

[64]  Marco Macchia,et al.  α‐Naphthylaminopropan‐2‐ol Derivatives as BACE1 Inhibitors , 2008, ChemMedChem.

[65]  M. Hung,et al.  Down-regulation of myeloid cell leukemia-1 through inhibiting Erk/Pin 1 pathway by sorafenib facilitates chemosensitization in breast cancer. , 2008, Cancer research.

[66]  T. Uchida,et al.  Pin1 is required for the Ser727 phosphorylation-dependent Stat3 activity , 2007, Oncogene.

[67]  R. Dalla‐Favera,et al.  Genotoxic stress regulates expression of the proto-oncogene Bcl6 in germinal center B cells , 2007, Nature Immunology.

[68]  S. Crovella,et al.  Pin1 promoter polymorphisms in hepatocellular carcinoma patients. , 2007, Gastroenterology.

[69]  M. Bowman,et al.  Structural basis for high-affinity peptide inhibition of human Pin1. , 2007, ACS chemical biology.

[70]  Elisabeth S Yeh,et al.  PIN1, the cell cycle and cancer , 2007, Nature Reviews Cancer.

[71]  L. Wahl,et al.  Functionally important residues in the peptidyl-prolyl isomerase Pin1 revealed by unigenic evolution. , 2007, Journal of molecular biology.

[72]  M. Hung,et al.  Degradation of Mcl-1 by β-TrCP Mediates Glycogen Synthase Kinase 3-Induced Tumor Suppression and Chemosensitization , 2006, Molecular and Cellular Biology.

[73]  Elisabeth S Yeh,et al.  The Loss of PIN1 Deregulates Cyclin E and Sensitizes Mouse Embryo Fibroblasts to Genomic Instability* , 2006, Journal of Biological Chemistry.

[74]  J. Diehl,et al.  Location, location, location: The role of cyclin D1 nuclear localization in cancer , 2005, Journal of cellular biochemistry.

[75]  K. Saxena,et al.  Polo-like Kinase 1-mediated Phosphorylation Stabilizes Pin1 by Inhibiting Its Ubiquitination in Human Cells* , 2005, Journal of Biological Chemistry.

[76]  A. Means,et al.  Peptidyl-Prolyl Isomerase 1 (Pin1) Serves as a Coactivator of Steroid Receptor by Regulating the Activity of Phosphorylated Steroid Receptor Coactivator 3 (SRC-3/AIB1) , 2005, Molecular and Cellular Biology.

[77]  Priti Garg,et al.  Modeling breast cancer in vivo and ex vivo reveals an essential role of Pin1 in tumorigenesis , 2004, The EMBO journal.

[78]  R. Mantovani,et al.  Pin1 links the activities of c-Abl and p300 in regulating p73 function. , 2004, Molecular cell.

[79]  J. Sowadski,et al.  Prevalent overexpression of prolyl isomerase Pin1 in human cancers. , 2004, The American journal of pathology.

[80]  Joseph R. Nevins,et al.  A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells , 2004, Nature Cell Biology.

[81]  A. Ryo,et al.  Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA. , 2003, Molecular cell.

[82]  Anna Frolov,et al.  The prolyl isomerase Pin1 is a novel prognostic marker in human prostate cancer. , 2003, Cancer research.

[83]  K. Lu.  Prolyl isomerase Pin1 as a molecular target for cancer diagnostics and therapeutics. , 2003, Cancer cell.

[84]  T. Uchida,et al.  Pin1 is overexpressed in oral squamous cell carcinoma and its levels correlate with cyclin D1 overexpression. , 2003, Oncology reports.

[85]  Sam W. Lee,et al.  PIN1 Is an E2F Target Gene Essential for Neu/Ras-Induced Transformation of Mammary Epithelial Cells , 2002, Molecular and Cellular Biology.

[86]  J. Noel,et al.  Critical Role of WW Domain Phosphorylation in Regulating Phosphoserine Binding Activity and Pin1 Function* , 2002, The Journal of Biological Chemistry.

[87]  T. Hunter,et al.  Loss of Pin1 function in the mouse causes phenotypes resembling cyclin D1-null phenotypes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[88]  Tianhua Niu,et al.  Pin1 is overexpressed in breast cancer and cooperates with Ras signaling in increasing the transcriptional activity of c‐Jun towards cyclin D1 , 2001, The EMBO journal.

[89]  W. El-Deiry,et al.  BRCA1 Effects on the Cell Cycle and the DNA Damage Response Are Linked to Altered Gene Expression* , 2000, The Journal of Biological Chemistry.

[90]  パトリック エム． エフ． ダークス，,et al.  Peptidyl prolyl cis - trans isomerase , 1999 .

[91]  R. Ranganathan,et al.  Structural and Functional Analysis of the Mitotic Rotamase Pin1 Suggests Substrate Recognition Is Phosphorylation Dependent , 1997, Cell.

[92]  T. Hunter,et al.  A human peptidyl–prolyl isomerase essential for regulation of mitosis , 1996, Nature.

[93]  George Parker,et al.  Notes on Some Cases from an Electrical Department , 1904, Bristol medico-chirurgical journal.

[94]  Therapeutic Memoranda , 1889, British medical journal.

[95]  P. Pandolfi,et al.  Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer , 2015, Nature Medicine.

[96]  Yu-nong Wu,et al.  The Pin1 gene polymorphism and the susceptibility of oral squamous cell carcinoma in East China. , 2014, Cancer biomarkers : section A of Disease markers.

[97]  J. Thomson,et al.  Structure-based design of novel human Pin1 inhibitors (II). , 2010, Bioorganic & medicinal chemistry letters.

[98]  T. Uchida,et al.  Pin 1 is required for the Ser 727 phosphorylation-dependent Stat 3 activity , 2007 .

[99]  Masafumi Nakamura,et al.  Pin1 regulates turnover and subcellular localization of β-catenin by inhibiting its interaction with APC , 2001, Nature Cell Biology.

[100]  W. J. Turrell.  Three Electrotherapists of the Eighteenth Century: John Wesley, Jean Paul Marat and James Graham* A Paper read before the Royal Society of Medicine Section of the History of Medicine, January 19, 1921. , 2022, Annals of medical history.