UCHL1

Summary

Gene Symbol: UCHL1
Description: ubiquitin C-terminal hydrolase L1
Alias: HEL-117, HEL-S-53, NDGOA, PARK5, PGP 9.5, PGP9.5, PGP95, SPG79, Uch-L1, ubiquitin carboxyl-terminal hydrolase isozyme L1, epididymis luminal protein 117, epididymis secretory protein Li 53, neuron cytoplasmic protein 9.5, ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase), ubiquitin thioesterase L1, ubiquitin thiolesterase
Species: human
Products:     UCHL1

Top Publications

  1. Saigoh K, Wang Y, Suh J, Yamanishi T, Sakai Y, Kiyosawa H, et al. Intragenic deletion in the gene encoding ubiquitin carboxy-terminal hydrolase in gad mice. Nat Genet. 1999;23:47-51 pubmed
    ..Here we find that the gad mutation is caused by an in-frame deletion including exons 7 and 8 of Uchl1, encoding the ubiquitin carboxy-terminal hydrolase (UCH) isozyme (Uch-l1) selectively expressed in the nervous ..
  2. Kabuta T, Furuta A, Aoki S, Furuta K, Wada K. Aberrant interaction between Parkinson disease-associated mutant UCH-L1 and the lysosomal receptor for chaperone-mediated autophagy. J Biol Chem. 2008;283:23731-8 pubmed publisher
  3. Zhang Z, Burgunder J, An X, Wu Y, Chen W, Zhang J, et al. Lack of evidence for association of a UCH-L1 S18Y polymorphism with Parkinson's disease in a Han-Chinese population. Neurosci Lett. 2008;442:200-2 pubmed publisher
    ..We did not observe any difference in allele or genotype frequencies between the cases and the controls (P>0.05). Our results do not support a role for this variant in sporadic PD. ..
  4. Okochi Takada E, Nakazawa K, Wakabayashi M, Mori A, Ichimura S, Yasugi T, et al. Silencing of the UCHL1 gene in human colorectal and ovarian cancers. Int J Cancer. 2006;119:1338-44 pubmed
    ..Among these was the UCHL1 gene (also known as PGP9.5), which is involved in regulation of cellular ubiquitin levels...
  5. Larsen C, Price J, Wilkinson K. Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues. Biochemistry. 1996;35:6735-44 pubmed
    ..6 microM). The binding is primarily electrostatic in nature and indicates the existence of a specific and extensive binding site for ubiquitin on the surface of the enzyme. ..
  6. Facheris M, Strain K, Lesnick T, de Andrade M, Bower J, Ahlskog J, et al. UCHL1 is associated with Parkinson's disease: a case-unaffected sibling and case-unrelated control study. Neurosci Lett. 2005;381:131-4 pubmed
    ..disequilibrium test to confirm the association of the S18Y variant of the ubiquitin carboxi-terminal hydrolase L1 (UCHL1) gene with Parkinson's disease (PD)...
  7. Xu E, Tang Y, Li D, Jia J. Polymorphism of HD and UCHL-1 genes in Huntington's disease. J Clin Neurosci. 2009;16:1473-7 pubmed publisher
    ..UCHL-1 S18Y polymorphism is a modifier of HD with a modest regulatory role in the age at disease onset, suggesting that UCHL-1 may be involved in HD pathogenesis. ..
  8. Das C, Hoang Q, Kreinbring C, Luchansky S, Meray R, Ray S, et al. Structural basis for conformational plasticity of the Parkinson's disease-associated ubiquitin hydrolase UCH-L1. Proc Natl Acad Sci U S A. 2006;103:4675-80 pubmed
    ..In particular, the geometry of the catalytic residues in the active site of UCH-L1 is distorted in such a way that the hydrolytic activity would appear to be impossible without substrate induced conformational rearrangements. ..
  9. Nazé P, Vuillaume I, Destee A, Pasquier F, Sablonniere B. Mutation analysis and association studies of the ubiquitin carboxy-terminal hydrolase L1 gene in Huntington's disease. Neurosci Lett. 2002;328:1-4 pubmed
    ..The S18Y polymorphism was found in three out of the four patients presenting with a later age-at-onset. We conclude that the UCH-L1 gene may be a genetic factor that influences the variability in age-at-onset of HD. ..

More Information

Publications86

  1. Bilguvar K, Tyagi N, Ozkara C, Tuysuz B, Bakircioglu M, Choi M, et al. Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration. Proc Natl Acad Sci U S A. 2013;110:3489-94 pubmed publisher
    Ubiquitin C-terminal hydrolase-L1 (UCHL1), a neuron-specific de-ubiquitinating enzyme, is one of the most abundant proteins in the brain...
  2. Larsen C, Krantz B, Wilkinson K. Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases. Biochemistry. 1998;37:3358-68 pubmed
  3. Cartier A, Djakovic S, Salehi A, Wilson S, Masliah E, Patrick G. Regulation of synaptic structure by ubiquitin C-terminal hydrolase L1. J Neurosci. 2009;29:7857-68 pubmed publisher
    ..These findings point to a significant role of UCH-L1 in synaptic remodeling, most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner. ..
  4. Costes S, Huang C, Gurlo T, Daval M, Matveyenko A, Rizza R, et al. β-cell dysfunctional ERAD/ubiquitin/proteasome system in type 2 diabetes mediated by islet amyloid polypeptide-induced UCH-L1 deficiency. Diabetes. 2011;60:227-38 pubmed publisher
    ..Our results indicate that defective protein degradation in β-cells in type 2 diabetes can, at least in part, be attributed to misfolded h-IAPP leading to UCH-L1 deficiency, which in turn further compromises β-cell viability. ..
  5. Park D, Nam M, Rhim H. The serine protease HtrA2 cleaves UCH-L1 and inhibits its hydrolase activity: implication in the UCH-L1-mediated cell death. Biochem Biophys Res Commun. 2011;415:24-9 pubmed publisher
    ..These findings suggest that the HtrA2-mediated cleavage of UCH-L1 may play important roles in regulating the fine balance between cell growth and cell death. ..
  6. Kyratzi E, Pavlaki M, Stefanis L. The S18Y polymorphic variant of UCH-L1 confers an antioxidant function to neuronal cells. Hum Mol Genet. 2008;17:2160-71 pubmed publisher
    ..Our results furthermore provide indirect evidence for the importance of oxidative stress as a pathogenetic factor in certain forms of sporadic PD. ..
  7. Blyth B, Farahvar A, He H, Nayak A, Yang C, Shaw G, et al. Elevated serum ubiquitin carboxy-terminal hydrolase L1 is associated with abnormal blood-brain barrier function after traumatic brain injury. J Neurotrauma. 2011;28:2453-62 pubmed publisher
    ..Ubiquitin C-terminal hydrolase 1 (UCHL1), and phosphorylated neurofilament heavy chain (pNF-H) are found exclusively in neurons, but their relationship to ..
  8. Mellick G, Silburn P. The ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism does not confer protection against idiopathic Parkinson's disease. Neurosci Lett. 2000;293:127-30 pubmed
    ..The frequency of the S18Y allele in Australian subjects is similar to that reported elsewhere. This study suggests that the S18Y polymorphism in UCH-L1 does not influence the risk for developing PD. ..
  9. Day I, Thompson R. Molecular cloning of cDNA coding for human PGP 9.5 protein. A novel cytoplasmic marker for neurones and neuroendocrine cells. FEBS Lett. 1987;210:157-60 pubmed
    ..Protein sequencing of 50% of PGP 9.5 confirms the deduced protein sequence. ..
  10. Elbaz A, Levecque C, Clavel J, Vidal J, Richard F, Corrèze J, et al. S18Y polymorphism in the UCH-L1 gene and Parkinson's disease: evidence for an age-dependent relationship. Mov Disord. 2003;18:130-7 pubmed
    ..In this community-based case-control study, carriers of the Y allele were at decreased risk of developing PD at a young age, independently of pesticides and smoking. ..
  11. Day I, Hinks L, Thompson R. The structure of the human gene encoding protein gene product 9.5 (PGP9.5), a neuron-specific ubiquitin C-terminal hydrolase. Biochem J. 1990;268:521-4 pubmed
    ..The human PGP9.5 gene, described here, spans 10 kb, contains nine exons and displays 5' features some common to many genes and some common with neurofilament neuron-specific enolase and Thy-1-antigen gene 5' regions. ..
  12. Frisan T, Coppotelli G, Dryselius R, Masucci M. Ubiquitin C-terminal hydrolase-L1 interacts with adhesion complexes and promotes cell migration, survival, and anchorage independent growth. FASEB J. 2012;26:5060-70 pubmed publisher
    ..These findings offer new insights on the molecular interactions through which the deubiquitinating enzyme regulates the survival, proliferation, and metastatic potential of malignant cells. ..
  13. Healy D, Abou Sleiman P, Wood N. Genetic causes of Parkinson's disease: UCHL-1. Cell Tissue Res. 2004;318:189-94 pubmed
    ..Important issues regarding UCHL-1 and its role in PD remain inconclusive, especially regarding the pathogenicity of the mendelian I93M mutation. This review tries to address some of these uncertainties. ..
  14. Hussain S, Foreman O, Perkins S, Witzig T, Miles R, van Deursen J, et al. The de-ubiquitinase UCH-L1 is an oncogene that drives the development of lymphoma in vivo by deregulating PHLPP1 and Akt signaling. Leukemia. 2010;24:1641-55 pubmed publisher
    ..These data provide the first in vivo evidence for DUB-driven oncogenesis and suggest that UCH-L1 hyperactivity deregulates normal Akt signaling. ..
  15. Karim R, Tummers B, Meyers C, Biryukov J, Alam S, Backendorf C, et al. Human papillomavirus (HPV) upregulates the cellular deubiquitinase UCHL1 to suppress the keratinocyte's innate immune response. PLoS Pathog. 2013;9:e1003384 pubmed publisher
    ..was shown to depend on hrHPV-induced expression of the cellular protein ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in keratinocytes...
  16. Snapinn K, Larson E, Kawakami H, Ujike H, Borenstein A, Izumi Y, et al. The UCHL1 S18Y polymorphism and Parkinson's disease in a Japanese population. Parkinsonism Relat Disord. 2011;17:473-5 pubmed publisher
    b>UCHL1 plays an important role in the ubiquitin-proteasome system and is a biologically plausible candidate gene for Parkinson's disease (PD)...
  17. Castegna A, Aksenov M, Aksenova M, Thongboonkerd V, Klein J, Pierce W, et al. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part I: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. Free Radic Biol Med. 2002;33:562-71 pubmed
    ..Proteomics offers a rapid means of identifying oxidatively modified proteins in aging and age-related neurodegenerative disorders without the limitations of the immunochemical detection method. ..
  18. Tokumaru Y, Yamashita K, Kim M, Park H, Osada M, Mori M, et al. The role of PGP9.5 as a tumor suppressor gene in human cancer. Int J Cancer. 2008;123:753-9 pubmed publisher
    ..Our data support the notion that PGP9.5 is a tumor suppressor gene that is inactivated by promoter methylation or gene deletion in several types of human cancers. ..
  19. Fukutomi S, Seki N, Koda K, Miyazaki M. Identification of methylation-silenced genes in colorectal cancer cell lines: genomic screening using oligonucleotide arrays. Scand J Gastroenterol. 2007;42:1486-94 pubmed
    ..After treatment, 350 genes were up-regulated 1.5-fold or more. Six genes (PAGE-5, VCX, MAEL, GAGED2, UCHL1, and GAGE7), which contained putative 5' CpG islands in their promoter regions, were confirmed to be silenced in ..
  20. Seliger B, Fedorushchenko A, Brenner W, Ackermann A, Atkins D, Hanash S, et al. Ubiquitin COOH-terminal hydrolase 1: a biomarker of renal cell carcinoma associated with enhanced tumor cell proliferation and migration. Clin Cancer Res. 2007;13:27-37 pubmed
    ..In addition, functional assays were done in generated transfectants. The ubiquitin COOH-terminal hydrolase L1 (UCHL1) was found to be differentially expressed in both RCC lesions and RCC cell lines and immunoreactive using patients'..
  21. Yasuda T, Nihira T, Ren Y, Cao X, Wada K, Setsuie R, et al. Effects of UCH-L1 on alpha-synuclein over-expression mouse model of Parkinson's disease. J Neurochem. 2009;108:932-44 pubmed publisher
    The rare inherited form of Parkinson's disease (PD), PARK5, is caused by a missense mutation in ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) gene, resulting in Ile93Met substitution in its gene product (UCH-L1(Ile93Met))...
  22. Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, et al. The ubiquitin pathway in Parkinson's disease. Nature. 1998;395:451-2 pubmed
  23. Lincoln S, Vaughan J, Wood N, Baker M, Adamson J, Gwinn Hardy K, et al. Low frequency of pathogenic mutations in the ubiquitin carboxy-terminal hydrolase gene in familial Parkinson's disease. Neuroreport. 1999;10:427-9 pubmed
    ..These changes are, therefore, unlikely to be pathogenic. We conclude that the I93M variant must either be a rare cause of disease or a harmless substitution whose occurrence in the family reflects a chance co-occurrence. ..
  24. Forero D, Benítez B, Arboleda G, Yunis J, Pardo R, Arboleda H. Analysis of functional polymorphisms in three synaptic plasticity-related genes (BDNF, COMT AND UCHL1) in Alzheimer's disease in Colombia. Neurosci Res. 2006;55:334-41 pubmed
    ..factor, BDNF Val66Met; catechol-O-methyl transferase, COMT Val158; ubiquitin carboxyl-terminal hydroxylase, UCHL1 S18Y) in a sample of 102 AD cases and 168 age and sex matched controls living in Bogotá, Colombia...
  25. Bheda A, Shackelford J, Pagano J. Expression and functional studies of ubiquitin C-terminal hydrolase L1 regulated genes. PLoS ONE. 2009;4:e6764 pubmed publisher
    ..One member of the UCH family, UCH L1, is expressed in a number of malignancies suggesting that this DUB might be involved in oncogenic processes, and ..
  26. Brinkmann K, Zigrino P, Witt A, Schell M, Ackermann L, Broxtermann P, et al. Ubiquitin C-terminal hydrolase-L1 potentiates cancer chemosensitivity by stabilizing NOXA. Cell Rep. 2013;3:881-91 pubmed publisher
    ..elegans cells. Our data identify the UCH-L1/NOXA interaction as a therapeutic target for overcoming cancer chemoresistance. ..
  27. Satoh J, Kuroda Y. A polymorphic variation of serine to tyrosine at codon 18 in the ubiquitin C-terminal hydrolase-L1 gene is associated with a reduced risk of sporadic Parkinson's disease in a Japanese population. J Neurol Sci. 2001;189:113-7 pubmed
  28. Healy D, Abou Sleiman P, Casas J, Ahmadi K, Lynch T, Gandhi S, et al. UCHL-1 is not a Parkinson's disease susceptibility gene. Ann Neurol. 2006;59:627-33 pubmed
    ..96 [95% confidence interval: 0.86-1.08], respectively), and a cumulative meta-analysis showed a trend toward a null effect. Based on the current evidence, the UCHL-1 gene does not exhibit a protective effect in PD. ..
  29. Koharudin L, Liu H, Di Maio R, Kodali R, Graham S, Gronenborn A. Cyclopentenone prostaglandin-induced unfolding and aggregation of the Parkinson disease-associated UCH-L1. Proc Natl Acad Sci U S A. 2010;107:6835-40 pubmed publisher
    ..Our findings suggest a possible mechanistic link between UCH-L1 modification by cyclopentenone prostaglandins and the etiology of neurodegeneration. ..
  30. Choi J, Levey A, Weintraub S, Rees H, Gearing M, Chin L, et al. Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson's and Alzheimer's diseases. J Biol Chem. 2004;279:13256-64 pubmed
    ..Together, these results provide evidence supporting a direct link between oxidative damage to the neuronal ubiquitination/de-ubiquitination machinery and the pathogenesis of sporadic AD and PD. ..
  31. Ragland M, Hutter C, Zabetian C, Edwards K. Association between the ubiquitin carboxyl-terminal esterase L1 gene (UCHL1) S18Y variant and Parkinson's Disease: a HuGE review and meta-analysis. Am J Epidemiol. 2009;170:1344-57 pubmed publisher
    The ubiquitin carboxyl-terminal esterase L1 gene, UCHL1, located on chromosome 4p14, has been studied as a potential candidate gene for Parkinson's disease risk...
  32. Trifa F, Karray Chouayekh S, Jmaa Z, Jmal E, Khabir A, Sellami Boudawara T, et al. Frequent CpG methylation of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in sporadic and hereditary Tunisian breast cancer patients: clinical significance. Med Oncol. 2013;30:418 pubmed publisher
    ..In this study, we aimed to assess, by methylation-specific PCR, the CpG methylation pattern of the UCHL1 promoter in 94 sporadic and 44 hereditary breast cancers from Tunisian patients...
  33. Zetterberg M, Sjölander A, von Otter M, Palmér M, Landgren S, Minthon L, et al. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y polymorphism in Alzheimer's disease. Mol Neurodegener. 2010;5:11 pubmed publisher
    ..Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a de-ubiquitinating enzyme with important functions in recycling of ubiquitin...
  34. Wang W, Li Q, Xu J, Cao X, Li H, Tang F, et al. Over-expression of ubiquitin carboxy terminal hydrolase-L1 induces apoptosis in breast cancer cells. Int J Oncol. 2008;33:1037-45 pubmed
    ..Our findings suggest that modulating the ubiquitination and deubiquitination pathway could be a novel method for tumor therapy. ..
  35. Kim Y, Lim S, Nam Y, Jeong J, Kim H, Lee K. Ubiquitin C-terminal hydrolase-L1 is a key regulator of tumor cell invasion and metastasis. Oncogene. 2009;28:117-27 pubmed publisher
    ..In Akt-negative mutants, overexpression of UCH-L1 does not affect the invasion and migration capability of H157 cells. These results suggest that UCH-L1 is a key molecule to regulate tumor-cell invasion by upstream activation of Akt. ..
  36. Yu J, Tao Q, Cheung K, Jin H, Poon F, Wang X, et al. Epigenetic identification of ubiquitin carboxyl-terminal hydrolase L1 as a functional tumor suppressor and biomarker for hepatocellular carcinoma and other digestive tumors. Hepatology. 2008;48:508-18 pubmed publisher
    The ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) is a carboxyl-terminal ubiquitin hydrolase regulating cellular ubiquitin levels, recently suggested as a tumor suppressor...
  37. Boudreaux D, Maiti T, Davies C, Das C. Ubiquitin vinyl methyl ester binding orients the misaligned active site of the ubiquitin hydrolase UCHL1 into productive conformation. Proc Natl Acad Sci U S A. 2010;107:9117-22 pubmed publisher
    Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a Parkinson disease-associated, putative cysteine protease found abundantly and selectively expressed in neurons...
  38. Mondello S, Papa L, Buki A, Bullock M, Czeiter E, Tortella F, et al. Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: a case control study. Crit Care. 2011;15:R156 pubmed publisher
  39. Leiblich A, Cross S, Catto J, Pesce G, Hamdy F, Rehman I. Human prostate cancer cells express neuroendocrine cell markers PGP 9.5 and chromogranin A. Prostate. 2007;67:1761-9 pubmed
  40. Harhangi B, Farrer M, Lincoln S, Bonifati V, Meco G, De Michele G, et al. The Ile93Met mutation in the ubiquitin carboxy-terminal-hydrolase-L1 gene is not observed in European cases with familial Parkinson's disease. Neurosci Lett. 1999;270:1-4 pubmed
    ..We conclude that the UCH-L1 gene is not a major gene responsible for familial PD. ..
  41. Caballero O, Resto V, Patturajan M, Meerzaman D, Guo M, Engles J, et al. Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1). Oncogene. 2002;21:3003-10 pubmed
    ..5 and JAB1 became more perinuclear and cytoplasmic in localization while p27(Kip1) was present only in the nucleus. Therefore, PGP9.5 may contribute to p27(Kip1) degradation via its interaction and nuclear translocation with JAB1. ..
  42. López Avalos M, Duvivier Kali V, Xu G, Bonner Weir S, Sharma A, Weir G. Evidence for a role of the ubiquitin-proteasome pathway in pancreatic islets. Diabetes. 2006;55:1223-31 pubmed
  43. Bifsha P, Landry K, Ashmarina L, Durand S, Seyrantepe V, Trudel S, et al. Altered gene expression in cells from patients with lysosomal storage disorders suggests impairment of the ubiquitin pathway. Cell Death Differ. 2007;14:511-23 pubmed
  44. Wang J, Zhao C, Si Y, Liu Z, Chen B, Yu L. ACT and UCH-L1 polymorphisms in Parkinson's disease and age of onset. Mov Disord. 2002;17:767-71 pubmed
    ..557 (95% C.I. = 0.314-0.985; P = 0.043). These data suggest that ACT polymorphism does not influence the risk for developing PD. UCH-L1 S18Y polymorphism, however, may be a weak protective factor against early-onset PD. ..
  45. Tan E, Puong K, Fook Chong S, Chua E, Shen H, Yuen Y, et al. Case-control study of UCHL1 S18Y variant in Parkinson's disease. Mov Disord. 2006;21:1765-8 pubmed
    ..meta-analysis observed a greater significant inverse association of the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y variant with Parkinson's disease (PD) for Asian (predominantly Japanese) populations compared with Caucasian ..
  46. Levecque C, Destee A, Mouroux V, Becquet E, Defebvre L, Amouyel P, et al. No genetic association of the ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism with familial Parkinson's disease. J Neural Transm (Vienna). 2001;108:979-84 pubmed
    ..This observation suggests that the previous positive results obtained may reflect mechanisms restricted to the sporadic form of the disease or to a founder effect of the disease susceptibility. ..
  47. Shi Q, Tao E. An Ile93Met substitution in the UCH-L1 gene is not a disease-causing mutation for idiopathic Parkinson's disease. Chin Med J (Engl). 2003;116:312-3 pubmed
    ..DNA was isolated from various blood samples using a phenolchloroform extraction. Ile93Met substitution was found neither in PD patients nor in controls. Our study suggested that Ile93Met of UCH-L1 gene did not influence risk of IPD. ..
  48. Edwards Y, Fox M, Povey S, Hinks L, Thompson R, Day I. The gene for human neurone specific ubiquitin C-terminal hydrolase (UCHL1, PGP9.5) maps to chromosome 4p14. Ann Hum Genet. 1991;55:273-8 pubmed
    Ubiquitin carboxy terminal hydrolase 1, UCHL1, is a neurone-specific protein involved in the ubiquitin-mediated proteolytic pathway...
  49. Kabuta T, Setsuie R, Mitsui T, Kinugawa A, Sakurai M, Aoki S, et al. Aberrant molecular properties shared by familial Parkinson's disease-associated mutant UCH-L1 and carbonyl-modified UCH-L1. Hum Mol Genet. 2008;17:1482-96 pubmed publisher
    ..Our results also suggest that the carbonyl modification of UCH-L1 and subsequent abnormal interactions of carbonyl-modified UCH-L1 with multiple proteins, including tubulin, constitute one of the causes of sporadic PD. ..
  50. Kagara I, Enokida H, Kawakami K, Matsuda R, Toki K, Nishimura H, et al. CpG hypermethylation of the UCHL1 gene promoter is associated with pathogenesis and poor prognosis in renal cell carcinoma. J Urol. 2008;180:343-51 pubmed publisher
    ..the renal cancer cell line ACHN treated with the demethylating agent 5-aza-2'-deoxycytidine and investigated the UCHL1 gene involved in the regulation of cellular ubiquitin levels...
  51. Li L, Tao Q, Jin H, Van Hasselt A, Poon F, Wang X, et al. The tumor suppressor UCHL1 forms a complex with p53/MDM2/ARF to promote p53 signaling and is frequently silenced in nasopharyngeal carcinoma. Clin Cancer Res. 2010;16:2949-58 pubmed publisher
    ..This study investigated the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in nasopharyngeal carcinoma pathogenesis...
  52. Nishikawa K, Li H, Kawamura R, Osaka H, Wang Y, Hara Y, et al. Alterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants. Biochem Biophys Res Commun. 2003;304:176-83 pubmed
    ..Taken together, these results suggest that further studies of altered UCH-L1 hydrolase function may provide new insights into a possible common pathogenic mechanism between familial and sporadic Parkinson's disease. ..
  53. Osaka H, Wang Y, Takada K, Takizawa S, Setsuie R, Li H, et al. Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron. Hum Mol Genet. 2003;12:1945-58 pubmed
    Mammalian neuronal cells abundantly express a deubiquitylating enzyme, ubiquitin carboxy-terminal hydrolase 1 (UCH L1). Mutations in UCH L1 are linked to Parkinson's disease as well as gracile axonal dystrophy (gad) in mice...
  54. Hsu S, Lai M, Er T, Yang S, Hung C, Tsai H, et al. Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) regulates the level of SMN expression through ubiquitination in primary spinal muscular atrophy fibroblasts. Clin Chim Acta. 2010;411:1920-8 pubmed publisher
    ..Our initial proteomics analysis discovered significant increase of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in type I SMA fibroblasts when compared to normal fibroblasts...
  55. Maraganore D, de Andrade M, Lesnick T, Farrer M, Bower J, Hardy J, et al. Complex interactions in Parkinson's disease: a two-phased approach. Mov Disord. 2003;18:631-6 pubmed
    ..of pathogenic mutations in the three genes alpha-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) has elucidated the ubiquitin proteasome system (UPS) and its potential role as a causal pathway in Parkinson's ..
  56. Andersson F, Werrell E, McMorran L, Crone W, Das C, Hsu S, et al. The effect of Parkinson's-disease-associated mutations on the deubiquitinating enzyme UCH-L1. J Mol Biol. 2011;407:261-72 pubmed publisher
  57. Xue S, Jia J. Genetic association between Ubiquitin Carboxy-terminal Hydrolase-L1 gene S18Y polymorphism and sporadic Alzheimer's disease in a Chinese Han population. Brain Res. 2006;1087:28-32 pubmed
    ..We conclude that Y allele and YY genotype of S18Y in the UCH-L1 gene may have a protective effect against sporadic AD in female subjects, probably due to altering the function of UCH-L1 and the interactions among different risk factors. ..
  58. Bheda A, Yue W, Gullapalli A, Whitehurst C, Liu R, Pagano J, et al. Positive reciprocal regulation of ubiquitin C-terminal hydrolase L1 and beta-catenin/TCF signaling. PLoS ONE. 2009;4:e5955 pubmed publisher
    ..Ubiquitin C-terminal Hydrolase L1 (UCH L1) has been linked to several neurological diseases as well as human cancer, but the physiological targets and the ..
  59. Tan E, Lu C, Peng R, Teo Y, Wu Chou Y, Chen R, et al. Analysis of the UCHL1 genetic variant in Parkinson's disease among Chinese. Neurobiol Aging. 2010;31:2194-6 pubmed publisher
    The inverse association of the functional ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y variant with Parkinson's disease (PD) among Caucasian populations has been debated...
  60. Savettieri G, De Marco E, Civitelli D, Salemi G, Nicoletti G, Annesi G, et al. Lack of association between ubiquitin carboxy-terminal hydrolase L1 gene polymorphism and PD. Neurology. 2001;57:560-1 pubmed
  61. Meray R, Lansbury P. Reversible monoubiquitination regulates the Parkinson disease-associated ubiquitin hydrolase UCH-L1. J Biol Chem. 2007;282:10567-75 pubmed
    ..Our results illustrate monoubiquitination as a reversible regulatory mechanism for DUB activity involving auto-deubiquitination. ..
  62. Carmine Belin A, Westerlund M, Bergman O, Nissbrandt H, Lind C, Sydow O, et al. S18Y in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) associated with decreased risk of Parkinson's disease in Sweden. Parkinsonism Relat Disord. 2007;13:295-8 pubmed
    ..The tyrosine variant was significantly inversely associated with PD (P=0.049) and with a low age of onset (50 years) (P=0.017) in the case-control material, supporting the hypothesis of a protective function. ..
  63. Doran J, Jackson P, Kynoch P, Thompson R. Isolation of PGP 9.5, a new human neurone-specific protein detected by high-resolution two-dimensional electrophoresis. J Neurochem. 1983;40:1542-7 pubmed
    ..This new neurone-specific cytoplasmic marker may prove useful in studies of neuronal development and in the detection of neuronal damage in disease of the nervous system. ..
  64. Hutter C, Samii A, Factor S, Nutt J, Higgins D, Bird T, et al. Lack of evidence for an association between UCHL1 S18Y and Parkinson's disease. Eur J Neurol. 2008;15:134-9 pubmed
    b>UCHL1 has been proposed as a candidate gene for Parkinson's disease (PD). A meta-analysis of white and Asian subjects reported an inverse association between the non-synonymous UCHL1 S18Y polymorphism and PD risk...
  65. Liu Y, Fallon L, Lashuel H, Liu Z, Lansbury P. The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility. Cell. 2002;111:209-18 pubmed
    ..Thus, the ligase activity as well as the hydrolase activity of UCH-L1 may play a role in proteasomal protein degradation, a critical process for neuronal health. ..
  66. Schröder C, Milde Langosch K, Gebauer F, Schmid K, Mueller V, Wirtz R, et al. Prognostic relevance of ubiquitin C-terminal hydrolase L1 (UCH-L1) mRNA and protein expression in breast cancer patients. J Cancer Res Clin Oncol. 2013;139:1745-55 pubmed publisher
    ..The data of our study suggest that high levels of UCH-L1 expression indicate a more aggressive tumour behaviour and might represent a potential target in breast cancer treatment. ..
  67. Wang L, Guo J, Nie L, Luo L, Zuo X, Shen L, et al. Case-control study of the UCH-L1 S18Y variant in sporadic Parkinson's disease in the Chinese population. J Clin Neurosci. 2011;18:541-4 pubmed publisher
  68. Brophy G, Mondello S, Papa L, Robicsek S, Gabrielli A, Tepas J, et al. Biokinetic analysis of ubiquitin C-terminal hydrolase-L1 (UCH-L1) in severe traumatic brain injury patient biofluids. J Neurotrauma. 2011;28:861-70 pubmed publisher
    ..This study shows a significant correlation between UCH-L1 CSF and serum median concentrations and biokinetics in severe TBI patients, and relationships with clinical outcome were detected. ..
  69. Maraganore D, Lesnick T, Elbaz A, Chartier Harlin M, Gasser T, Kruger R, et al. UCHL1 is a Parkinson's disease susceptibility gene. Ann Neurol. 2004;55:512-21 pubmed
    The reported inverse association between the S18Y variant of the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene and Parkinson's disease (PD) has strong biological plausibility...
  70. Wu Y, Chen C, Chen Y, Chao C, Ro L, Fung H, et al. Ubiquitin specific proteases USP24 and USP40 and ubiquitin thiolesterase UCHL1 polymorphisms have synergic effect on the risk of Parkinson's disease among Taiwanese. Clin Chim Acta. 2010;411:955-8 pubmed publisher
    ..the association of ubiquitin specific proteases USP24 rs487230 C>T, USP40 rs1048603 C>T, and ubiquitin thiolesterase UCHL1 rs5030732 A>C polymorphisms with the risk of PD...
  71. Ardley H, Scott G, Rose S, Tan N, Robinson P. UCH-L1 aggresome formation in response to proteasome impairment indicates a role in inclusion formation in Parkinson's disease. J Neurochem. 2004;90:379-91 pubmed
    ..Furthermore, UCH-L1 accumulation is likely to play a pathological role in inclusion formation in Parkinson's disease. ..
  72. Rolen U, Kobzeva V, Gasparjan N, Ovaa H, Winberg G, Kisseljov F, et al. Activity profiling of deubiquitinating enzymes in cervical carcinoma biopsies and cell lines. Mol Carcinog. 2006;45:260-9 pubmed
    ..UCH-L1, UCH-L3, USP7, and USP9X activity was upregulated following HPV E6/E7 immortalization of keratinocytes, suggesting a role of these enzymes in growth transformation. ..
  73. Fujikane T, Nishikawa N, Toyota M, Suzuki H, Nojima M, Maruyama R, et al. Genomic screening for genes upregulated by demethylation revealed novel targets of epigenetic silencing in breast cancer. Breast Cancer Res Treat. 2010;122:699-710 pubmed publisher
    ..Thus, DNA methylation appears to be a common event in breast cancer, and the genes silenced by methylation could be useful targets for both diagnosis and therapy. ..
  74. Mastoraki A, Ioannidis E, Patsouris E, Safioleas M, Aroni K. PGP 9.5 expression in cutaneous keratoacanthomas and squamous cell carcinomas. Arch Dermatol Res. 2009;301:653-8 pubmed publisher
    ..PGP 9.5 expression proved closely associated with tumor aggressiveness and is classified as a marker for predicting the outcome of resection-treated skin cancer patients. ..
  75. Carolan B, Heguy A, Harvey B, Leopold P, Ferris B, Crystal R. Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers. Cancer Res. 2006;66:10729-40 pubmed
    ..Of 11 genes considered to be neuroendocrine cell specific, only ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a member of the ubiquitin proteasome pathway, was consistently up-regulated in smokers compared with nonsmokers...
  76. Mizukami H, Shirahata A, Goto T, Sakata M, Saito M, Ishibashi K, et al. PGP9.5 methylation as a marker for metastatic colorectal cancer. Anticancer Res. 2008;28:2697-700 pubmed
    ..029). These findings indicated that PGP9.5 was less frequently methylated in metastatic colorectal cancer, suggesting that PGP9.5 hypomethylation might play an important role in re-expression of the PGP9.5 gene in colorectal cancer. ..
  77. Takami Y, Nakagami H, Morishita R, Katsuya T, Cui T, Ichikawa T, et al. Ubiquitin carboxyl-terminal hydrolase L1, a novel deubiquitinating enzyme in the vasculature, attenuates NF-kappaB activation. Arterioscler Thromb Vasc Biol. 2007;27:2184-90 pubmed
    We identified a ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene, which encodes a deubiquitinating enzyme and is expressed in the vasculature, by functional screening of a human endothelial cell (EC) cDNA library...