Ubiquitin C‑terminal hydrolase‑L1: A new cancer marker and therapeutic target with dual effects (Review)

Ubiquitin C-terminal hydrolase-L1 (UCH-L1), a member of the lesser-known deubiquitinating enzyme family, has deubiquitinase and ubiquitin (Ub) ligase activity and the role of stabilizing Ub. UCH-L1 was first discovered in the brain and is associated with regulating cell differentiation, proliferation, transcriptional regulation and numerous other biological processes. UCH-L1 is predominantly expressed in the brain and serves a role in tumor promotion or inhibition. There is still controversy about the effect of UCH-L1 dysregulation in cancer and its mechanisms are unknown. Extensive research to investigate the mechanism of UCH-L1 in different types of cancer is key for the future treatment of UCH-L1-associated cancer. The present review details the molecular structure and function of UCH-L1. The role of UCH-L1 in different types of cancer is also summarized and how novel treatment targets provide a theoretical foundation in cancer research is discussed.

[1]  Meng Jia,et al.  Ubiquitin C-terminal hydrolase-L1 expression in non-small-cell lung cancer and its association with clinicopathological features and prognosis , 2021, Virchows Archiv.

[2]  D. Butterfield Ubiquitin carboxyl-terminal hydrolase L-1 in brain: Focus on its oxidative/nitrosative modification and role in brains of subjects with Alzheimer disease and mild cognitive impairment. , 2021, Free radical biology & medicine.

[3]  Edward W. Tate,et al.  UCHL1 as a novel target in breast cancer: emerging insights from cell and chemical biology , 2021, British Journal of Cancer.

[4]  Aditya R. Thawani,et al.  Activity-based protein profiling reveals deubiquitinase and aldehyde dehydrogenase targets of a cyanopyrrolidine probe , 2021, RSC medicinal chemistry.

[5]  B. Baradaran,et al.  Up-down regulation of HIF-1α in cancer progression. , 2021, Gene.

[6]  N. Chang,et al.  Upregulation of KCNMA1 facilitates the reversal effect of verapamil on the chemoresistance to cisplatin of esophageal squamous cell carcinoma cells. , 2021, European review for medical and pharmacological sciences.

[7]  Stephen N. Jones,et al.  Mdm2 phosphorylation by Akt regulates the p53 response to oxidative stress to promote cell proliferation and tumorigenesis , 2021, Proceedings of the National Academy of Sciences.

[8]  M. Azad,et al.  CRISPR-mediated modification of DNA methylation pattern in the new era of cancer therapy. , 2020, Epigenomics.

[9]  H. Ovaa,et al.  Small-Molecule Activity-Based Probe for Monitoring Ubiquitin C-Terminal Hydrolase L1 (UCHL1) Activity in Live Cells and Zebrafish Embryos , 2020, Journal of the American Chemical Society.

[10]  Zhigang Zhang,et al.  Plakoglobin is involved in cytoskeletal rearrangement of podocytes under the regulation of UCH-L1. , 2020, Biochemical and biophysical research communications.

[11]  Xiaoyan Wang,et al.  Ubiquitin C‐terminal hydrolase L1 promotes expression of programmed cell death‐ligand 1 in non‐small‐cell lung cancer cells , 2020, Cancer Science.

[12]  Edward W. Tate,et al.  Discovery of a Potent and Selective Covalent Inhibitor and Activity-Based Probe for the Deubiquitylating Enzyme UCHL1, with Antifibrotic Activity , 2019, Journal of the American Chemical Society.

[13]  H. Piao,et al.  UCHL1 enhances the malignant development of glioma via targeting GAS2. , 2020, European review for medical and pharmacological sciences.

[14]  Hongde Liu,et al.  Ubiquitin Carboxyl-Terminal Hydrolases (UCHs): Potential Mediators for Cancer and Neurodegeneration , 2020, International journal of molecular sciences.

[15]  Yuting Gu,et al.  The deubiquitinating enzyme UCHL1 promotes resistance to pemetrexed in non-small cell lung cancer by upregulating thymidylate synthase , 2020, Theranostics.

[16]  Y. Fujikawa,et al.  The evolutionarily conserved deubiquitinase UBH1/UCH-L1 augments DAF7/TGF-β signaling, inhibits dauer larva formation, and enhances lung tumorigenesis , 2020, The Journal of Biological Chemistry.

[17]  Hui-Hua Li,et al.  The deubiquitinase UCHL1 regulates cardiac hypertrophy by stabilizing epidermal growth factor receptor , 2020, Science Advances.

[18]  W. Dębek,et al.  Ubiquitin carboxy‐terminal hydrolase L1 – physiology and pathology , 2020, Cell Biochemistry and Function.

[19]  Yingqin Li,et al.  Hypermethylation of UCHL1 Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN) , 2020, Cells.

[20]  A. Venkitaraman,et al.  Pulsatile MAPK Signaling Modulates p53 Activity to Control Cell Fate Decisions at the G2 Checkpoint for DNA Damage , 2020, Cell reports.

[21]  S. Mok,et al.  Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) Promotes Uterine Serous Cancer Cell Proliferation and Cell Cycle Progression , 2020, Cancers.

[22]  Y. Tao,et al.  UCH-L1-mediated Down-regulation of Estrogen Receptor α Contributes to Insensitivity to Endocrine Therapy for Breast Cancer , 2020, Theranostics.

[23]  Sylvia E. Le Dévédec,et al.  Deubiquitinase Activity Profiling Identifies UCHL1 as a Candidate Oncoprotein That Promotes TGFβ-Induced Breast Cancer Metastasis , 2019, Clinical Cancer Research.

[24]  J. Minna,et al.  Ubiquitin C‐terminal hydrolase‐L1 has prognostic relevance and is a therapeutic target for high‐grade neuroendocrine lung cancers , 2019, Cancer science.

[25]  Senye Takahashi,et al.  Ubiquitin carboxyl‐terminal hydrolase L1 promotes hypoxia‐inducible factor 1‐dependent tumor cell malignancy in spheroid models , 2019, Cancer Science.

[26]  K. Roux,et al.  A cysteine near the C-terminus of UCH-L1 is dispensable for catalytic activity but is required to promote AKT phosphorylation, eIF4F assembly, and malignant B-cell survival , 2019, Cell Death Discovery.

[27]  C. Post,et al.  Ubiquitin C‐Terminal Hydrolase L1: Biochemical and Cellular Characterization of a Covalent Cyanopyrrolidine‐Based Inhibitor , 2019, ChemBioChem.

[28]  Peng Li,et al.  Synergistic effect of paclitaxel and verapamil to overcome multi-drug resistance in breast cancer cells. , 2019, Biochemical and biophysical research communications.

[29]  S. Kondo,et al.  Inhibition of UCH-L1 Deubiquitinating Activity with Two Forms of LDN-57444 Has Anti-Invasive Effects in Metastatic Carcinoma Cells , 2019, International journal of molecular sciences.

[30]  D. Edwards,et al.  UCHL1 loss alters the cell-cycle in metastatic pancreatic neuroendocrine tumors. , 2019, Endocrine-related cancer.

[31]  Lieping Chen,et al.  A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization , 2019, Cell.

[32]  Sarah H. Johnson,et al.  UCH-L1 bypasses mTOR to promote protein biosynthesis and is required for MYC-driven lymphomagenesis in mice. , 2018, Blood.

[33]  Zhixiang Wu,et al.  The deubiquitinating enzyme UCHL1 is a favorable prognostic marker in neuroblastoma as it promotes neuronal differentiation , 2018, Journal of experimental & clinical cancer research : CR.

[34]  R. Weinberg,et al.  New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer , 2018, Nature reviews. Molecular cell biology.

[35]  Xinxing Wang,et al.  Ubiquitin Carboxyl Terminal Hydrolase L1 Attenuates TNF-α-Mediated Vascular Smooth Muscle Cell Migration Through Suppression of NF-κB Activation. , 2018, International heart journal.

[36]  R. Trojanec,et al.  Genetic Markers in Triple‐Negative Breast Cancer , 2018, Clinical breast cancer.

[37]  J. Ornato,et al.  Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study , 2018, The Lancet Neurology.

[38]  K. Kristiansen,et al.  CRISPR/Cascade 9-Mediated Genome Editing-Challenges and Opportunities , 2018, Front. Genet..

[39]  Takashi Minegishi,et al.  High Expression of Ubiquitin C-terminal Hydrolase L1 Is Associated With Poor Prognosis in Endometrial Cancer Patients , 2018, International Journal of Gynecologic Cancer.

[40]  Kelong Ma,et al.  Upregulation of Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) Mediates the Reversal Effect of Verapamil on Chemo-Resistance to Adriamycin of Hepatocellular Carcinoma , 2018, Medical science monitor : international medical journal of experimental and clinical research.

[41]  M. Duffy,et al.  Mutant p53 in breast cancer: potential as a therapeutic target and biomarker , 2018, Breast Cancer Research and Treatment.

[42]  Jin-Ming Yang,et al.  UCH‐L1 promotes invasion of breast cancer cells through activating Akt signaling pathway , 2018, Journal of cellular biochemistry.

[43]  T. Limpaiboon,et al.  Aberrant methylation of HTATIP2 and UCHL1 as a predictive biomarker for cholangiocarcinoma. , 2017, Molecular medicine reports.

[44]  D. Lane,et al.  Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others , 2018, Nature Reviews Clinical Oncology.

[45]  H. Daraee,et al.  Verapamil (VER) Enhances the Cytotoxic Effects of Docetaxel and Vinblastine Combined Therapy Against Non-Small Cell Lung Cancer Cell Lines , 2017, Drug Research.

[46]  Xizhong Shen,et al.  Ubiquitin carboxyl-terminal hydrolases: involvement in cancer progression and clinical implications , 2017, Cancer and Metastasis Reviews.

[47]  Dong Hun Lee,et al.  UCHL1 Regulates Melanogenesis through Controlling MITF Stability in Human Melanocytes. , 2017, The Journal of investigative dermatology.

[48]  Xu Sun,et al.  UCH‐L1‐containing exosomes mediate chemotherapeutic resistance transfer in breast cancer , 2017, Journal of surgical oncology.

[49]  Hongmao Zhang,et al.  UCH-L1 Inhibition Suppresses tau Aggresome Formation during Proteasomal Impairment , 2017, Molecular Neurobiology.

[50]  G. Sarkis,et al.  Ubiquitin C-terminal hydrolase-L1 (UCH-L1) as a therapeutic and diagnostic target in neurodegeneration, neurotrauma and neuro-injuries , 2017, Expert opinion on therapeutic targets.

[51]  Ji-hong Cui,et al.  UCH-L1 Expressed by Podocytes: a Potentially Therapeutic Target for Lupus Nephritis? , 2017, Inflammation.

[52]  Wen-juan Wang,et al.  Overexpression of ubiquitin carboxyl terminal hydrolase‐L1 enhances multidrug resistance and invasion/metastasis in breast cancer by activating the MAPK/Erk signaling pathway , 2016, Molecular carcinogenesis.

[53]  J. Henley,et al.  Ubiquitin C-terminal hydrolase L1 (UCH-L1): structure, distribution and roles in brain function and dysfunction , 2016, The Biochemical journal.

[54]  A. Feldman,et al.  UCH-L1 is induced in germinal center B cells and identifies patients with aggressive germinal center diffuse large B-cell lymphoma. , 2016, Blood.

[55]  Min Xie,et al.  UCH-L1 Inhibition Decreases the Microtubule-Binding Function of Tau Protein. , 2015, Journal of Alzheimer's disease : JAD.

[56]  A. Khabir,et al.  CpG methylation of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) and P53 mutation pattern in sporadic colorectal cancer , 2016, Tumor Biology.

[57]  P. L. Bergsagel,et al.  UCHL1 is a biomarker of aggressive multiple myeloma required for disease progression , 2015, Oncotarget.

[58]  Xiaoshan Feng,et al.  The Diagnosis Value of Promoter Methylation of UCHL1 in the Serum for Progression of Gastric Cancer , 2015, BioMed research international.

[59]  Wei Zhang,et al.  UCH-L1 involved in regulating the degradation of EGFR and promoting malignant properties in drug-resistant breast cancer. , 2015, International journal of clinical and experimental pathology.

[60]  Mei Zhao,et al.  The de-ubiquitinase UCHL1 promotes gastric cancer metastasis via the Akt and Erk1/2 pathways , 2015, Tumor Biology.

[61]  L. Tang,et al.  Heterogeneous expression and biological function of ubiquitin carboxy-terminal hydrolase-L1 in osteosarcoma. , 2015, Cancer letters.

[62]  S. Linder,et al.  Deubiquitinase inhibition as a cancer therapeutic strategy. , 2015, Pharmacology & therapeutics.

[63]  M. Sonobe,et al.  UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1α , 2015, Nature Communications.

[64]  Weihong Song,et al.  Overexpression of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) delays Alzheimer's progression in vivo , 2014, Scientific Reports.

[65]  V. Lang,et al.  The Ubiquitin-Proteasome System (UPS) as a Cancer Drug Target: Emerging Mechanisms and Therapeutics , 2014, Stress Response Pathways in Cancer.

[66]  S. Balabanov,et al.  UCH-L1 induces podocyte hypertrophy in membranous nephropathy by protein accumulation. , 2014, Biochimica et biophysica acta.

[67]  T. L. Thuoc,et al.  Ubiquitin carboxyl hydrolase L1 significance for human diseases. , 2014, Protein and peptide letters.

[68]  L. Marchionni,et al.  Association of Promoter Methylation of VGF and PGP9.5 with Ovarian Cancer Progression , 2013, PloS one.

[69]  H. Schlüter,et al.  Prognostic relevance of ubiquitin C-terminal hydrolase L1 (UCH-L1) mRNA and protein expression in breast cancer patients , 2013, Journal of Cancer Research and Clinical Oncology.

[70]  Yu Sun,et al.  The regulation of the UCH-L1 gene by transcription factor NF-κB in podocytes. , 2013, Cellular signalling.

[71]  K. Uchida,et al.  Ubiquitin C-terminal Hydrolase L1 (UCH-L1) Acts as a Novel Potentiator of Cyclin-dependent Kinases to Enhance Cell Proliferation Independently of Its Hydrolase Activity* , 2013, The Journal of Biological Chemistry.

[72]  Michael J. Schell,et al.  Ubiquitin C-terminal hydrolase-L1 potentiates cancer chemosensitivity by stabilizing NOXA. , 2013, Cell reports.

[73]  Mei Zhao,et al.  UCHL1 acts as a colorectal cancer oncogene via activation of the β-catenin/TCF pathway through its deubiquitinating activity. , 2012, International journal of molecular medicine.

[74]  David Komander,et al.  Atypical ubiquitylation — the unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages , 2012, Nature Reviews Molecular Cell Biology.

[75]  T. Putti,et al.  The Ubiquitin Peptidase UCHL1 Induces G0/G1 Cell Cycle Arrest and Apoptosis Through Stabilizing p53 and Is Frequently Silenced in Breast Cancer , 2012, PloS one.

[76]  M. Sumura,et al.  Tumor Suppressor Function of PGP9.5 Is Associated with Epigenetic Regulation in Prostate Cancer—Novel Predictor of Biochemical Recurrence after Radical Surgery , 2012, Cancer Epidemiology, Biomarkers & Prevention.

[77]  S. Balabanov,et al.  Ubiquitin C-terminal hydrolase-l1 activity induces polyubiquitin accumulation in podocytes and increases proteinuria in rat membranous nephropathy. , 2011, The American journal of pathology.

[78]  Ivan Dikic,et al.  The spatial and temporal organization of ubiquitin networks , 2011, Nature Reviews Molecular Cell Biology.

[79]  S. H. Baek,et al.  UCH-L1 promotes cancer metastasis in prostate cancer cells through EMT induction. , 2011, Cancer letters.

[80]  M. Herrero,et al.  Expression in the mammalian retina of parkin and UCH-L1, two components of the ubiquitin-proteasome system , 2010, Brain Research.

[81]  S. Perkins,et al.  The de-ubiquitinase UCH-L1 is an oncogene that drives the development of lymphoma in vivo by deregulating PHLPP1 and Akt signaling , 2010, Leukemia.

[82]  X. Shen,et al.  The potential role of ubiquitin c-terminal hydrolases in oncogenesis. , 2010, Biochimica et biophysica acta.

[83]  W. Jia,et al.  The Tumor Suppressor UCHL1 Forms a Complex with p53/MDM2/ARF to Promote p53 Signaling and Is Frequently Silenced in Nasopharyngeal Carcinoma , 2010, Clinical Cancer Research.

[84]  Ian N. M. Day,et al.  UCHL1 (PGP 9.5): Neuronal biomarker and ubiquitin system protein , 2010, Progress in Neurobiology.

[85]  M. Caplow,et al.  Ubiquitin editing enzyme UCH L1 and microtubule dynamics: Implication in mitosis , 2010, Cell cycle.

[86]  Xiaoyu Dong,et al.  Ubiquitin carboxyl terminal hydrolase L1 negatively regulates TNFalpha-mediated vascular smooth muscle cell proliferation via suppressing ERK activation. , 2010, Biochemical and biophysical research communications.

[87]  T. O'Brien,et al.  Therapeutic strategies within the ubiquitin proteasome system , 2010, Cell Death and Differentiation.

[88]  B. Seliger,et al.  Epigenetic control of the ubiquitin carboxyl terminal hydrolase 1 in renal cell carcinoma , 2009, Journal of Translational Medicine.

[89]  M. Masucci,et al.  The ubiquitin C‐terminal hydrolase UCH‐L1 regulates B‐cell proliferation and integrin activation , 2009, Journal of cellular and molecular medicine.

[90]  David Komander,et al.  Breaking the chains: structure and function of the deubiquitinases , 2009, Nature Reviews Molecular Cell Biology.

[91]  W. Yue,et al.  Positive Reciprocal Regulation of Ubiquitin C-Terminal Hydrolase L1 and β-Catenin/TCF Signaling , 2009, PloS one.

[92]  E. Patsouris,et al.  PGP 9.5 expression in cutaneous keratoacanthomas and squamous cell carcinomas , 2009, Archives of Dermatological Research.

[93]  Qi Chen,et al.  UCH‐L1 expression of podocytes in diseased glomeruli and in vitro , 2009, The Journal of pathology.

[94]  B. Teh,et al.  Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma. , 2009, The Journal of clinical endocrinology and metabolism.

[95]  Y. M. Kim,et al.  Ubiquitin C-terminal hydrolase-L1 is a key regulator of tumor cell invasion and metastasis , 2009, Oncogene.

[96]  K. Wada,et al.  Aberrant Interaction between Parkinson Disease-associated Mutant UCH-L1 and the Lysosomal Receptor for Chaperone-mediated Autophagy* , 2008, Journal of Biological Chemistry.

[97]  D. Sidransky,et al.  The role of PGP9.5 as a tumor suppressor gene in human cancer , 2008, International journal of cancer.

[98]  Jun Yu,et al.  Epigenetic identification of ubiquitin carboxyl‐terminal hydrolase L1 as a functional tumor suppressor and biomarker for hepatocellular carcinoma and other digestive tumors , 2008, Hepatology.

[99]  N. Seki,et al.  CpG hypermethylation of the UCHL1 gene promoter is associated with pathogenesis and poor prognosis in renal cell carcinoma. , 2008, The Journal of urology.

[100]  K. Uchida,et al.  Aberrant molecular properties shared by familial Parkinson's disease-associated mutant UCH-L1 and carbonyl-modified UCH-L1. , 2008, Human molecular genetics.

[101]  Jin-Ming Yang,et al.  Over-expression of ubiquitin carboxy terminal hydrolase-L1 induces apoptosis in breast cancer cells. , 2008, International journal of oncology.

[102]  T. Ogihara,et al.  Ubiquitin Carboxyl-Terminal Hydrolase L1, a Novel Deubiquitinating Enzyme in the Vasculature, Attenuates NF-&kgr;B Activation , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[103]  H. Ovaa,et al.  Profiling proteasome activity in tissue with fluorescent probes. , 2007, Molecular pharmaceutics.

[104]  Rieko Setsuie,et al.  The functions of UCH-L1 and its relation to neurodegenerative diseases , 2007, Neurochemistry International.

[105]  G. Cuny,et al.  Structure-activity relationship, kinetic mechanism, and selectivity for a new class of ubiquitin C-terminal hydrolase-L1 (UCH-L1) inhibitors. , 2007, Bioorganic & medicinal chemistry letters.

[106]  E. Leznik,et al.  The role of ubiquitin C-terminal hydrolase L1 in neurodegenerative disorders. , 2007, Drug news & perspectives.

[107]  Tudor A. Fulga,et al.  Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo , 2007, Nature Cell Biology.

[108]  P. Lansbury,et al.  Substrate recognition and catalysis by UCH-L1. , 2006, Biochemistry.

[109]  S. Ichinose,et al.  Localization of ubiquitin C-terminal hydrolase L1 in mouse ova and its function in the plasma membrane to block polyspermy. , 2006, The American journal of pathology.

[110]  T. Ushijima,et al.  Silencing of the UCHL1 gene in human colorectal and ovarian cancers , 2006, International journal of cancer.

[111]  D. Sidransky,et al.  PGP9.5 methylation in diffuse-type gastric cancer. , 2006, Cancer research.

[112]  Gregory A Petsko,et al.  Structural basis for conformational plasticity of the Parkinson's disease-associated ubiquitin hydrolase UCH-L1. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[113]  Yoichi Tanaka,et al.  PGP9.5 promoter methylation is an independent prognostic factor for esophageal squamous cell carcinoma. , 2005, Cancer research.

[114]  S. Eccles,et al.  Breast cancer metastasis: when, where, how? , 2005, The Lancet.

[115]  K. Mimori,et al.  Promoter Methylation Is an Independent Prognostic Factor for Esophageal Squamous Cell Carcinoma , 2005 .

[116]  Tsutomu Ohta,et al.  Overexpression of cortactin is involved in motility and metastasis of hepatocellular carcinoma. , 2004, Journal of hepatology.

[117]  T Takano,et al.  PGP9.5 mRNA could contribute to the molecular-based diagnosis of medullary thyroid carcinoma. , 2004, European journal of cancer.

[118]  Peter T Lansbury,et al.  Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line. , 2003, Chemistry & biology.

[119]  Kaori Nishikawa,et al.  Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron. , 2003, Human molecular genetics.

[120]  H. Rochefort,et al.  How to target estrogen receptor-negative breast cancer? , 2003, Endocrine-related cancer.

[121]  T. Hirokawa,et al.  Alterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants. , 2003, Biochemical and biophysical research communications.

[122]  P. Lansbury,et al.  The UCH-L1 Gene Encodes Two Opposing Enzymatic Activities that Affect α-Synuclein Degradation and Parkinson's Disease Susceptibility , 2002, Cell.

[123]  Georg Auburger,et al.  The ubiquitin pathway in Parkinson's disease , 1998, Nature.

[124]  K D Wilkinson,et al.  Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases. , 1998, Biochemistry.

[125]  K D Wilkinson,et al.  Crystal structure of a deubiquitinating enzyme (human UCH‐L3) at 1.8 å resolution , 1997, The EMBO journal.

[126]  K D Wilkinson,et al.  The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. , 1989, Science.

[127]  R. Thompson,et al.  Isolation of PGP 9.5, a New Human Neurone‐Specific Protein Detected by High‐Resolution Two‐Dimensional Electrophoresis , 1983, Journal of neurochemistry.