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| serpinsSummarySummary: A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known. Top Publications
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Publications
Conformational pathology of the serpins: themes, variations, and therapeutic strategiesBibek Gooptu
School of Crystallography, Birkbeck College, University of London, London, UK
Annu Rev Biochem 78:147-76. 2009..Polymers of serpins can also form in extracellular tissues where they activate inflammatory cascades...
Pigment epithelium-derived factor: a potent inhibitor of angiogenesisD W Dawson
Department of Microbiology Immunology, Department of Pathology, Robert H Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, IL 60611, USA
Science 285:245-8. 1999..These results suggest that PEDF may be of therapeutic use, especially in retinopathies where pathological neovascularization compromises vision and leads to blindness...
Serpin structure, mechanism, and functionPeter G W Gettins
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, M/C 536, 1819-53 West Polk Street, Chicago, Illinois 60612, USA
Chem Rev 102:4751-804. 2002
Characterization of PEDF: a multi-functional serpin family proteinS Filleur
Department of Urology, Texas Tech University Health Sciences Center, 3601 4th Street, MS 6591, Lubbock, Texas 79430 6591, USA
J Cell Biochem 106:769-75. 2009....
Overexpression of pigment epithelium-derived factor decreases angiogenesis and inhibits the growth of human malignant melanoma cells in vivoRiichiro Abe
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Am J Pathol 164:1225-32. 2004..PEDF therefore might be a promising novel therapeutic agent for treatment of patients with melanoma...
The paradoxical expression of maspin in ovarian carcinomaAnil K Sood
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Iowa, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242 1109, USA
Clin Cancer Res 8:2924-32. 2002..These paradoxical results may offer new insights regarding the role of maspin in ovarian cancer progression that may also impact diagnosis and treatment strategies...
Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cellsZ Zou
Division of Cancer Genetics, Dana Farber Cancer Institute, Boston, MA 02115
Science 263:526-9. 1994..Analysis of human breast cancer specimens revealed that loss of maspin expression occurred most frequently in advanced cancers. These results support the hypothesis that maspin functions as a tumor suppressor...
Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active siteHua Liu
Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD 21287 8984, USA
Proc Natl Acad Sci U S A 101:6605-10. 2004..Furthermore, PEDF may represent a superior therapeutic approach to sepsis-associated hypotension, nephrotic syndrome, and other sight-threatening and life-threatening diseases resulting from excessive vascular permeability...
Two functional epitopes of pigment epithelial-derived factor block angiogenesis and induce differentiation in prostate cancerStephanie Filleur
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
Cancer Res 65:5144-52. 2005..Our results map active regions for the two PEDF functions, signaling via distinct receptors, identify candidate peptides, and provide their mechanism of action for future development of PEDF-based tumor therapies...
Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factorLuigi Notari
National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 281:38022-37. 2006....
Pigment epithelium-derived factor (PEDF) is an endogenous antiinflammatory factorSarah X Zhang
Department of Medicine Endocrinology, Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
FASEB J 20:323-5. 2006..These findings suggest that PEDF is a novel endogenous anti-inflammatory factor in the eye. The decrease of ocular PEDF levels may contribute to inflammation and vascular leakage in DR...
Pigment epithelium-derived factor downregulates vascular endothelial growth factor (VEGF) expression and inhibits VEGF-VEGF receptor 2 binding in diabetic retinopathySarah X Zhang
Department of Medicine, Department of Cell Biology, University of Oklahoma Health Sciences Center, 941 Stanton L Young Blvd, Oklahoma City, OK, USA
J Mol Endocrinol 37:1-12. 2006..The decrease in PEDF levels in the retina is at least partially responsible for the increase in VEGF expression and subsequent vascular leakage and neovascularization in diabetes...
Serpins flex their muscle: I. Putting the clamps on proteolysis in diverse biological systemsGary A Silverman
Department of Pediatrics and Cell Biology and Physiology, Children s Hospital of Pittsburgh and Magee Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15201, USA
J Biol Chem 285:24299-305. 2010b>Serpins compose the largest superfamily of peptidase inhibitors and are well known as regulators of hemostasis and thrombolysis...
Nuclear cytokine-activated IKKalpha controls prostate cancer metastasis by repressing MaspinJun Li Luo
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0723, USA
Nature 446:690-4. 2007..We propose that tumour-infiltrating RANKL-expressing cells lead to nuclear IKKalpha activation and inhibition of Maspin transcription, thereby promoting the metastatic phenotype...
Pigment epithelium-derived factor suppresses ischemia-induced retinal neovascularization and VEGF-induced migration and growthElia J Duh
Department of Ophthalmology, Johns Hopkins University School of Medicine, Maumenee 809, 600 N. Wolfe Street, Baltimore, MD 21287, USA
Invest Ophthalmol Vis Sci 43:821-9. 2002..These findings suggest that localized administration of PEDF may be an effective approach for the treatment of ischemia-induced retinal neovascular disorders...
Pigment epithelium-derived factor behaves like a noninhibitory serpin. Neurotrophic activity does not require the serpin reactive loopS P Becerra
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 270:25992-9. 1995..Altogether our data indicate that PEDF belongs to the subgroup of noninhibitory serpins and that its N-terminal region confers a neurite-promoting activity to the protein...
Focus on Molecules: Pigment epithelium-derived factor (PEDF)S Patricia Becerra
NIH-NEI, 7 Memorial Drive, Room 304, Building 7, Bethesda, MD 20892, USA
Exp Eye Res 82:739-40. 2006
Biological functions of maspinCaleb M Bailey
Department of Anatomy and Cell Biology, The Carver College of Medicine, University of Iowa, Iowa City, IA, USA
J Cell Physiol 209:617-24. 2006....
PEDF: a multifaceted neurotrophic factorJoyce Tombran-Tink
Division of Pharmaceutical Sciences, University of Missouri-Kansas City, 5005 Rockhill Road, Kansas City, Missouri 64110, USA
Nat Rev Neurosci 4:628-36. 2003
Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium-derived factor in a xenograft modelLisa P Abramson
Division of Pediatric Surgery, Children s Memorial Hospital, and the Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA
J Pediatr Surg 38:336-42; discussion 336-42. 2003..The authors postulated that systemic administration of PEDF would decrease Wilms' tumor growth in a xenograft model, and increased renal vascularity would result in a mouse null for PEDF...
Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degenerationImran A Bhutto
Department of Ophthalmology, The Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287-9115, USA
Exp Eye Res 82:99-110. 2006..The decrease in PEDF may disrupt the balance and be permissive for the formation of choroidal neovascularization (CNV) in AMD...
STAT6 activation by Toxoplasma gondii infection induces the expression of Th2 C-C chemokine ligands and B clade serine protease inhibitors in macrophageHye Jin Ahn
Department of Parasitology and the Catholic Institute of Parasitic Diseases, College of Medicine, Catholic University of Korea, Seoul 137 701, South Korea
Parasitol Res 105:1445-53. 2009..It also mediated expression of two large clusters of C-C chemokine ligands (CCLs) and serine protease inhibitors (SERPINs) in microarray of T. gondii-infected macrophages...
Pigment epithelium-derived factor inhibits angiogenesis via regulated intracellular proteolysis of vascular endothelial growth factor receptor 1Jun Cai
School of Optometry and Vision Sciences, Cardiff University, UK
J Biol Chem 281:3604-13. 2006..This confirms the importance of PEDF and VEGFR-1 in the negative regulation of angiogenesis...
Structure-function relationships of PEDFT Kawaguchi
Department of Digestive Disease Information and Research and Department of Medicine, Kurume University School of Medicine, Kurume 830 0011, Japan
Curr Mol Med 10:302-11. 2010..In addition, since PEDF is recently identified as a regulator for glucose and lipid metabolism, we also discuss PEDF structures specially related to insulin-sensitizing and triglyceridereducing properties...
Increased serum pigment epithelium derived factor levels in Type 2 diabetes patientsAlicia Jenkins
Department of Medicine, Endocrinology, Harold Hamm Oklahoma Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Diabetes Res Clin Pract 82:e5-7. 2008..3 (2.8) vs. 3.2 (2.0)mug/ml, p<0.001. In diabetes, PEDF correlated with BMI, serum creatinine and LDL-cholesterol, but not with other lipids, HbA1c or CRP. PEDF did not differ by drugs, complications, or gender...
Alterations of retinal pigment epithelium cause AMD-like retinopathy in senescence-accelerated OXYS ratsAnton M Markovets
Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
Aging (Albany NY) 3:44-54. 2011..These data suggest that primary cellular degenerative alterations in the RPE cells secondarily lead to choriocapillaris atrophy and results in complete loss of photoreceptor cells in the OXYS rats' retina by the age of 24 months...
Overexpression of pigment epithelium-derived factor inhibits retinal inflammation and neovascularizationKyoungmin Park
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
Am J Pathol 178:688-98. 2011..The PEDF-Tg mice provide a useful model for studying the roles of angiogenic inhibitors in neovascular disorders such as diabetic retinopathy...
Expression of maspin predicts poor prognosis in breast-cancer patientsYoshihisa Umekita
Department of Pathology, Faculty of Medicine, Kagoshima University, Sakuragaoka, Kagoshima, Japan
Int J Cancer 100:452-5. 2002....
Probing neuroserpin polymerization and interaction with amyloid-beta peptides using single molecule fluorescenceAlbert Chiou
Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
Biophys J 97:2306-15. 2009..The A beta(1-40) is displaced from the complex so that it acts as a catalyst and is not incorporated into neuroserpin polymers...
Constitutive overexpression of pigment epithelium-derived factor inhibition of ocular melanoma growth and metastasisHua Yang
Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Invest Ophthalmol Vis Sci 51:28-34. 2010..This study investigates whether constitutive overexpression of PEDF inhibits the growth and hepatic micrometastasis of ocular melanoma...
Granzyme M is a regulatory protease that inactivates proteinase inhibitor 9, an endogenous inhibitor of granzyme BSami Mahrus
Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, California 94143 2280, USA
J Biol Chem 279:54275-82. 2004..Finally, the interaction between granzyme M and the serpins alpha(1)-antichymotrypsin, alpha(1)-proteinase inhibitor, and proteinase inhibitor 9 was characterized by using a ..
Expression of the p53 and Maspin protein in primary prostate cancer: correlation with clinical featuresS Machtens
Department of Urology, Hannover University Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
Int J Cancer 95:337-42. 2001..Our investigation delivers first hints for a p53-dependent regulatory pathway of the Maspin protein in human prostate cancer...
Blocking tumor growth, invasion, and metastasis by maspin in a syngeneic breast cancer modelH Y Shi
Baylor College of Medicine, Department of Molecular and Cellular Biology, Houston, Texas 77030, USA
Cancer Res 61:6945-51. 2001..Thus, maspin can block primary tumor growth as well as invasion and metastasis. These data support the concept that maspin has a strong protective role against tumor progression...
Novel mechanism for age-related macular degeneration: an equilibrium shift between the angiogenesis factors VEGF and PEDFK Ohno-Matsui
Department of Ophthalmology and Visual Science, Graduate School, Tokyo Medical and Dental University, Yushima, Bunkyo ku, Tokyo, Japan
J Cell Physiol 189:323-33. 2001..This equilibrium shift may be significant in promoting a pathological condition of RPE cells and contributing to choroidal neovascularization in age-related macular degeneration...
Expression of the tumor suppressor gene Maspin in human pancreatic cancersN Maass
Department of Gynecologic Oncology, University of Kiel, 24105 Kiel, Germany
Clin Cancer Res 7:812-7. 2001..In addition, the detection of maspin in pancreatic tumor tissues and its lack of expression in all normal pancreatic tissues suggests that maspin may be a useful marker of primary human pancreatic cancer...
Expression of the granzyme B inhibitor, protease inhibitor 9, by tumor cells in patients with non-Hodgkin and Hodgkin lymphoma: a novel protective mechanism for tumor cells to circumvent the immune system?Bellinda A Bladergroen
Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands
Blood 99:232-7. 2002..Expression of this inhibitor is yet another mechanism used by tumor cells to escape their elimination by cytotoxic lymphocytes...
Decreased pigment epithelium-derived factor expression in human breast cancer progressionJun Cai
Cell and Molecular Biology Group, School of Optometry and Vision Sciences, Wales College of Medicine, Cardiff University, United Kingdom
Clin Cancer Res 12:3510-7. 2006..The aim of this study was to correlate the expression of pigment epithelium-derived factor (PEDF), a potent endogenous antiangiogenic molecule, with severity and prognosis in breast cancer...
Pigment epithelium-derived factor inhibits TNF-alpha-induced interleukin-6 expression in endothelial cells by suppressing NADPH oxidase-mediated reactive oxygen species generationSho ichi Yamagishi
Department of Internal Medicine III, Kurume University School of Medicine, Kurume 830 0011, Japan
J Mol Cell Cardiol 37:497-506. 2004..Our present study suggests that PEDF may play an important role in the development and progression of atherosclerosis...
Identification of the neuroprotective molecular region of pigment epithelium-derived factor and its binding sites on motor neuronsMasako M Bilak
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
J Neurosci 22:9378-86. 2002..The data support the pharmacotherapeutic potential of PEDF as a neuroprotectant in human motor neuron degeneration...
Pigment epithelium-derived factor is a substrate for matrix metalloproteinase type 2 and type 9: implications for downregulation in hypoxiaLuigi Notari
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-0607, USA
Invest Ophthalmol Vis Sci 46:2736-47. 2005..These results reveal a novel posttranslational mechanism for downregulating PEDF, and provide an explanation for hypoxia-provoked increases in VEGF/PEDF ratios, in angiogenesis and/or in neuronal death...
Pigment epithelium-derived factor inhibits oxidative stress-induced apoptosis and dysfunction of cultured retinal pericytesShinjiro Amano
Department of Internal Medicine III, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
Microvasc Res 69:45-55. 2005..Our present study suggests that substitution of PEDF proteins might be a promising therapeutic strategy for treatment of patients with early diabetic retinopathy...
PEDF: a potential molecular therapeutic target with multiple anti-cancer activitiesEugene T H Ek
Department of Orthopaedics, University of Melbourne St. Vincent's Hospital, Melbourne, PO Box 2900, Fitzroy, Melbourne, Australia
Trends Mol Med 12:497-502. 2006..We also discuss the prospects for PEDF therapy and the need for a closer evaluation of issues such as delivery, stability and potential toxicity...
Pigment epithelium-derived factor delays the death of photoreceptors in mouse models of inherited retinal degenerationsM Cayouette
Faculte de Medecine, Centre de Recherche Universite Laval Robert Giffard, 2601, de la Canardière, Beauport, Quebec, G1J 2G3, Canada
Neurobiol Dis 6:523-32. 1999..We conclude that PEDF can act as a survival-promoting factor for photoreceptors in vivo and could potentially be useful for the treatment of photoreceptor diseases...
A serpin that regulates immune melanization in the respiratory system of DrosophilaHuaping Tang
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA
Dev Cell 15:617-26. 2008..Such signaling between local and systemic immune responses could represent an alarm mechanism that prepares the host in case a pathogen breaches epithelial defenses to invade internal tissues...
Protective immunity against Ixodes ricinus induced by a salivary serpinP P Prevot
Institut de Biologie et de Médecine Moléculaires, Universite Libre de Bruxelles, rue des Professeurs Jeener et Brachet, 12, B 6041 Gosselies, Belgium
Vaccine 25:3284-92. 2007..It belongs to the superfamily of serpins and interferes with both haemostasis and the immune response of the host...
Corneal angiogenic privilege: angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing (an American Ophthalmological Society thesis)Dimitri T Azar
Massachusetts Eye and Ear Infirmary and Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA
Trans Am Ophthalmol Soc 104:264-302. 2006....
Analysis of novel disease-related genes in bronchial asthmaNoriko Yuyama
Genox Research, Inc. Kawasaki, Japan
Cytokine 19:287-96. 2002..In a complex disorder such as asthma, this combination of in vitro and in vivo genomic approaches is a powerful discriminatory method enabling identification of novel disease-related genes and their mechanisms of regulation...
Neuroserpin polymers activate NF-kappaB by a calcium signaling pathway that is independent of the unfolded protein responseMark J Davies
Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust Medical Research Council Building, Hills Road, Cambridge CB2 0XY, United Kingdom
J Biol Chem 284:18202-9. 2009..This pathway provides a mechanism for cells to sense and react to the accumulation of folded structures of mutant serpins within the endoplasmic reticulum...
Plasma pigment epithelium-derived factor is positively associated with obesity in Caucasian subjects, in particular with the visceral fat depotPing Wang
Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands
Eur J Endocrinol 159:713-8. 2008....
Interaction of activated protein C with serpinsJ M Hermans
Department of Haematology, University of Cambridge, MRC Centre, U K
Biochem J 295:239-45. 1993The inhibition of activated protein C by six different serine protease inhibitors (serpins) that have arginine residues in the P1 position has been investigated...
Pigment epithelium-derived factor regulates the vasculature and mass of the prostate and pancreasJennifer A Doll
Department of Pathology, Northwestern University Medical School, 303 E Chicago Ave, Chicago, Illinois, 60611, USA
Nat Med 9:774-80. 2003..Thus, PEDF regulates normal pancreas and prostate mass. Its androgen sensitivity makes PEDF a likely contributor to the anticancer effects of androgen ablation...
Anti-angiogenic pigment epithelium-derived factor regulates hepatocyte triglyceride content through adipose triglyceride lipase (ATGL)Chuhan Chung
Department of Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
J Hepatol 48:471-8. 2008..We postulated that hepatocyte triglyceride metabolism was dependent on interactions between PEDF and ATGL, and loss of PEDF would impair mobilization of triglycerides in the liver...
Pigment epithelium-derived factor contributes to insulin resistance in obesitySeamus Crowe
Department of Physiology, Monash University, Clayton, Victoria 3800, Australia
Cell Metab 10:40-7. 2009..Overall, these results identify a causal role for PEDF in obesity-induced insulin resistance...
Maspin expression and localization impact on angiogenesis and prognosis in ovarian cancerL A Solomon
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wayne State University, Karmanos Cancer Institute, Harper Professional Building, 4160 John R St, Suite 2127, Detroit, MI 48201, USA
Gynecol Oncol 101:385-9. 2006..CONCLUSION: Maspin expression and localization seem to play a role in ovarian cancer angiogenesis and progression. High nuclear expression was associated with reduced markers of angiogenesis and prolonged survival...
Pigment epithelium-derived factor (PEDF) is one of the most abundant proteins secreted by human adipocytes and induces insulin resistance and inflammatory signaling in muscle and fat cellsS Famulla
Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Dusseldorf, Germany
Int J Obes (Lond) 35:762-72. 2011..The aim of this study was to investigate the regulation and autocrine function of PEDF in human adipocytes and to determine its paracrine effects on human skeletal muscle cells (hSkMC) and human smooth muscle cells (hSMC)...
Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functionsJames C Whisstock
From the Department of Biochemistry and Molecular Biology and ARC Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria 3800, Australia
J Biol Chem 285:24307-12. 2010Inhibitory serpins are metastable proteins that undergo a substantial conformational rearrangement to covalently trap target peptidases...
Regulation of factors controlling angiogenesis in liver development: a role for PEDF in the formation and maintenance of normal vasculatureS Sawant
Pharmaceutical Sciences, University of Missouri Kansas City, Kansas City, MO, USA
Biochem Biophys Res Commun 325:408-13. 2004..The VEGF isoforms 121 and 189 may be key regulators of increased vascularity and progression of hepatocellular carcinoma, one of the most common malignant tumors, and may be of prognostic significance for this tumor...
Decreased pigment epithelium-derived factor is associated with metastatic phenotype in human and rat prostate tumorsSofia Halin
Department of Medical Biosciences, Umea University, Umea, Sweden
Cancer Res 64:5664-71. 2004..These observations indicate that loss of pigment epithelium-derived factor expression could be associated with the progression toward a metastatic phenotype in prostate cancer...
Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesityKazuyuki Hida
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama 700 8558, Japan
Proc Natl Acad Sci U S A 102:10610-5. 2005..These findings indicate that vaspin exerts an insulin-sensitizing effect targeted toward WATs in states of obesity...
Prognostic significance of maspin in pancreatic ductal adenocarcinoma: tissue microarray analysis of 223 surgically resected casesDengfeng Cao
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
Mod Pathol 20:570-8. 2007....
Loss of maspin is a helpful prognosticator in colorectal cancer: a tissue microarray analysisCarsten Boltze
Department of Pathology, University of Rostock, Strempelstrasse 14, Rostock D 18055, Germany
Pathol Res Pract 200:783-90. 2005..The determination of the immunohistochemical expression status of maspin might be a helpful independent prognosticator and an applicable tool for the development of therapeutic strategies for patients with this disease...
Maspin inhibits cell migration in the absence of protease inhibitory activityRosemary Bass
School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, United Kingdom
J Biol Chem 277:46845-8. 2002..It is devoid of activity against a wide range of proteases, in common with other non-inhibitory serpins, but has recently been reported to inhibit plasminogen activators associated with cells and other biological ..
Arabidopsis AtSerpin1, crystal structure and in vivo interaction with its target protease RESPONSIVE TO DESICCATION-21 (RD21)Nardy Lampl
Department of Plant Sciences, Weizmann Institute of Science, Rehovot 76100, Israel
J Biol Chem 285:13550-60. 2010..b>Serpins feature a reactive center loop (RCL), which displays a protease target sequence as a bait...
p53 regulates the expression of the tumor suppressor gene maspinZ Zou
Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA
J Biol Chem 275:6051-4. 2000....
Nuclear expression of maspin is associated with a lower recurrence rate and a longer disease-free interval after surgery for squamous cell carcinoma of the larynxG Marioni
Department of Otolaryngology, Head and Neck Surgery, University of Padua, Padua, Italy
Histopathology 46:576-82. 2005..Only two studies concerning maspin expression in head and neck carcinomas are available. The present study is the first attempt to determine maspin expression in laryngeal carcinoma...
The neutrophil serine protease inhibitor serpinb1 preserves lung defense functions in Pseudomonas aeruginosa infectionCharaf Benarafa
CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
J Exp Med 204:1901-9. 2007..Thus, regulation of pulmonary innate immunity by serpinb1 is nonredundant and is required to protect two key components, the neutrophil and SP-D, from NSP damage during the host response to infection...
Blocking the Wnt pathway, a unifying mechanism for an angiogenic inhibitor in the serine proteinase inhibitor familyBin Zhang
Department of Cell Biology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Proc Natl Acad Sci U S A 107:6900-5. 2010..These results suggest that SERPINA3K is a high-affinity, endogenous antagonist of LRP6. The blockade of Wnt signaling may represent a unifying mechanism for the anti-inflammatory and anti-angiogenic effects of SERPINA3K...
Antiangiogenic effects and transcriptional regulation of pigment epithelium-derived factor in diabetic retinopathyBinhui Wang
Vascular Medicine, School of Graduate Entry Medicine and Health, University of Nottingham, Nottingham, UK
Microvasc Res 80:31-6. 2010..Gene expression of PEDF is negatively regulated by glucose, insulin (via an mTOR-dependent pathway) and VEGF...
High expression levels of IKKalpha and IKKbeta are necessary for the malignant properties of liver cancerRunqiu Jiang
Liver Transplantation Center of the First Affiliated Hospital and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu Province, People s Republic of China
Int J Cancer 126:1263-74. 2010..We anticipate that IKK-targeted gene therapy can be used in the treatment of HCC, a cancer that is notoriously resistant to radiation and chemotherapy...
Pigment epithelium-derived factor maintains retinal pigment epithelium function by inhibiting vascular endothelial growth factor-R2 signaling through gamma-secretaseZsolt Ablonczy
Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
J Biol Chem 284:30177-86. 2009....
Maspin expression in myoepithelial tumors of the breastJ S Reis-Filho
Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP, Portugal
Pathol Res Pract 197:817-21. 2001....
Maspin modulates prostate cancer cell apoptotic and angiogenic response to hypoxia via targeting AKTS McKenzie
Division of Urology, Department of Surgery, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY 40536, USA
Oncogene 27:7171-9. 2008..This study may have significance in the identification of maspin-driven therapeutic targeting in advanced metastatic prostate cancer...
Shape-shifting serpins--advantages of a mobile mechanismJames A Huntington
University of Cambridge, Department of Haematology, Cambridge Institute for Medical Research, Division of Structural Medicine, Thrombosis Research Unit, Wellcome Trust MRC Building, Hills Road, Cambridge, CB2 2XY, UK
Trends Biochem Sci 31:427-35. 2006b>Serpins use an extraordinary mechanism of protease inhibition that depends on a rapid and marked conformational change and causes destruction of the covalently linked protease...
Maspin expression inhibits osteolysis, tumor growth, and angiogenesis in a model of prostate cancer bone metastasisMichael L Cher
Department of Urology, Protease Program, and Integrated Biostatistics Unit, The Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA
Proc Natl Acad Sci U S A 100:7847-52. 2003....
Tick-Encoded serine proteinase inhibitors (serpins); potential target antigens for tick vaccine developmentA Muleng
Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan
J Vet Med Sci 63:1063-9. 2001....
Maspin: the new frontierZhila Khalkhali-Ellis
Children s Memorial Research Center, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60614 3394, USA
Clin Cancer Res 12:7279-83. 2006..This perspective briefly outlines the past and present strides in deciphering this unique molecule and speculates on new frontiers in maspin research and prospects of maspin as a diagnostic/prognostic indicator in cancer...
Aberrant methylation of the maspin promoter is an early event in human breast cancerBernard W Futscher
Bone Marrow Transplant Program, Arizona Cancer Center, and Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ 85724, USA
Neoplasia 6:380-9. 2004..Taken together, these results indicate that aberrant methylation of the maspin promoter is an early event in human breast cancer...
Elevated nuclear maspin expression is associated with microsatellite instability and high tumour grade in colorectal cancerMarcus Bettstetter
Department of Pathology, University of Regensburg, D-93053 Regensburg, Germany
J Pathol 205:606-14. 2005..013), de-differentiated tumours (p = 0.006), and at the invasion front. These findings provide new insights into the role of maspin in colorectal cancer progression and may be useful for diagnosis and treatment strategies...
Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis. Comparison with the main clinical and pathological prognostic factorsR Molina
Laboratory of Clinical Biochemistry, Unit for Cancer Research, Hospital Clinic, Barcelona, Spain
Tumour Biol 24:209-18. 2003..Eighty-five percent of the patients with SCC levels >2 ng/ml had squamous tumors. Likewise, CA 125 levels <60 U/ml or CEA <10 ng/ml excluded adenocarcinoma or LCLC with a probability of 82 and 91%, respectively...
Maspin functions as tumor suppressor by increasing cell adhesion to extracellular matrix in prostate tumor cellsShaji Abraham
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA
J Urol 169:1157-61. 2003....
Co-expression of the squamous cell carcinoma antigens 1 and 2 in normal adult human tissues and squamous cell carcinomasS Cataltepe
Division of Newborn Medicine, Children s Hospital, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115 5737, USA
J Histochem Cytochem 48:113-22. 2000..these data indicated that the expression of SCCA1 and SCCA2 was not restricted to the squamous epithelium and that these serpins may coordinately regulate cysteine and serine proteinase activity in both normal and transformed tissues.
FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosisA M Chinnaiyan
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA
Cell 81:505-12. 1995..These findings suggest that FADD may play an important role in the proximal signal transduction of Fas...
Heterologous expression of three plant serpins with distinct inhibitory specificitiesS W Dahl
Department of Biochemistry and Nutrition, Technical University of Denmark, DK 2800 Lyngby, Denmark
J Biol Chem 271:25083-8. 1996For the first time, inhibitory plant serpins, including WSZ1 from wheat, BSZ4, and the previously unknown protein BSZx from barley, have been expressed in Escherichia coli, and a procedure for fast purification of native plant serpins ..
Expression of Maspin in non-muscle invasive bladder carcinoma: correlation with tumor angiogenesis and prognosisMartin G Friedrich
Department of Urology, University of Hamburg, University Hospital Hamburg Eppendorf, Martinistr 52, D 20246 Hamburg, Germany
Eur Urol 45:737-43. 2004..We studied expression patterns of Maspin in pTa/pT1 urothelial carcinoma of the bladder and compared them with microvessel density (MVD) for two vascular markers (CD34 and CD105) and correlated the findings with clinical outcome...
Maspin expression, angiogenesis, prognostic parameters, and outcome in malignant melanomaRamon Chua
Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
J Am Acad Dermatol 60:758-66. 2009..However, it has been correlated with malignant behavior in pancreatic and ovarian cancer. The role of maspin in malignant melanoma (MM) has not yet been systematically examined...
Maspin overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human ovarian carcinomaFiliz Bolat
Baskent University Faculty of Medicine, Department of Pathology, Ankara, Turkey
Pathol Res Pract 204:379-87. 2008..These results may offer new insights regarding the role of maspin in ovarian cancer and might also affect the diagnosis and treatment strategies...
Anaphylactic release of mucosal mast cell granule proteases: role of serpins in the differential clearance of mouse mast cell proteases-1 and -2Alan D Pemberton
Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, United Kingdom
J Immunol 176:899-904. 2006..mMCP-1 isolated from serum is complexed with serpins and we conclude that both the accumulation and the longevity of mMCP-1 in blood is due to complex formation, ..
Nuclear Maspin expression is associated with response to adjuvant 5-fluorouracil based chemotherapy in patients with stage III colon cancerWolfgang Dietmaier
Department of Pathology and Molecular Diagnostics, University of Regensburg, Germany
Int J Cancer 118:2247-54. 2006..Patients with negative immunohistochemical Maspin expression do not benefit from 5-FU treatment and may be candidates for an alternative (non-5-FU based) adjuvant therapy regime...
Inhibition of soluble recombinant furin by human proteinase inhibitor 8J R Dahlen
Department of Pathology, University of New Mexico School of Medicine, Albuquerque 87131, USA
J Biol Chem 273:1851-4. 1998....
Loss of maspin is a negative prognostic factor for invasion and metastasis in oral squamous cell carcinomaKunio Yoshizawa
Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan
J Oral Pathol Med 38:535-9. 2009..In this study, we investigated the interrelationship between clinicopathologic findings and maspin expression in oral squamous cell carcinoma (OSCC)...
Molecular cloning and expression of an intracellular serpin: an elastase inhibitor from horse leucocytesT Kordula
Institute of Molecular Biology, Jagiellionian University, Krakow, Poland
Biochem J 293:187-93. 1993..Transformed bacteria expressed significant amounts of the protein, which was immunoprecipitated with a specific anti-HLEI antiserum. Furthermore, HLEI expressed in bacteria inhibited the activity of elastase but not trypsin...
Diagnostic and prognostic significance of squamous cell carcinoma antigen in non-small cell lung cancerT Vassilakopoulos
Department of Critical Care and Pulmonary Services, Evangelismos Hospital, University of Athens Medical School, Athens, Greece
Lung Cancer 32:137-44. 2001..In conclusion, the SCC-Ag serum level has moderate diagnostic role in NSCLC. Both the preoperative SCC-Ag level and its postoperative decrease have prognostic significance, yet inferior to the disease stage and the patient's age...
Evidence for a direct interaction between the tumor suppressor serpin, maspin, and types I and III collagenOliver E Blacque
Department of Biochemistry and Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
J Biol Chem 277:10783-8. 2002..A direct interaction between exogenous or cell surface maspin and extracellular matrix collagen may contribute to a cell adhesion role in the prevention of tumor cell migration and angiogenesis...
Down regulation of the tumor suppressor gene maspin in breast carcinoma is associated with a higher risk of distant metastasisN Maass
Department of Obstetrics and Gynecology, Department of Gynecologic Oncology, University of Kiel, Michaelisstrasse 16, 24105 Kiel, Germany
Clin Biochem 34:303-7. 2001....
Tipping the balance for angiogenic disordersGuoquan Gao
Drug Discov Today 7:171-2. 2002
Angiostatin decreases cell migration and vascular endothelium growth factor (VEGF) to pigment epithelium derived factor (PEDF) RNA ratio in vitro and in a murine ocular melanoma modelHua Yang
Departments of Ophthalmology, Emory University School of Medicine, Atlanta, GA 30322, USA
Mol Vis 12:511-7. 2006..Angiostatin significantly decreases the ratio of VEGF/PEDF mRNA level in vitro and in hepatic micrometastatic melanoma cells. Angiostatin increases PEDF mRNA in melanoma metastases...
[The molecular mechanisms of neovascular age-related macular degeneration]D W Miller
Universitäts Augenklinik Heidelberg
Ophthalmologe 100:92-6. 2003..This article describes current research in the pathophysiology of choroidal neovascularization secondary to age-related macular degeneration...
[Pharmacological therapy for age-related macular degeneration. Current developments and perspectives]F G Holz
Universitäts Augenklinik Heidelberg
Ophthalmologe 100:97-103. 2003..Other targets include the inhibition of toxic compound formation in lipofuscin granules such as AZ-E. What follows is an overview of different substances and their stages of development in clinical trials...
Antiangiogenic gene therapy for hepatocellular carcinoma using angiostatin geneHiroki Ishikawa
First Department of Internal Medicine, Nagasaki University School of Medicine, and Health Research Center, Nagasaki University, Nagasaki, Japan
Hepatology 37:696-704. 2003..In conclusion, antiangiogenic gene therapy using angiostatin gene is potentially suitable for the treatment of patients with HCC...
[Cytokines and microangiopathy]Masanobu Kawakami
Department of Comprehensive Medicine, Jichi Medical School Omiya Medical Center
Nippon Rinsho 63:79-84. 2005
Vascular endothelial growth factor upregulates pigment epithelium-derived factor expression via VEGFR-1 in human retinal pigment epithelial cellsKyoko Ohno-Matsui
Department of Ophthalmology and Visual Science, Graduate School, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8519, Japan
Biochem Biophys Res Commun 303:962-7. 2003..These results demonstrate a regulatory interaction between angiogenesis stimulators and inhibitors to maintain homeostasis in normal human retina...
Research Grants
- A Role of Novel Serpin Maspinin Prostate Tumor/Bone InteractionShijie Sheng; Fiscal Year: 2010..point of view, the activity of maspin to target serine protease-like molecules may not be substituted by other serpins that have evolved to acquire higher target specificities...
- MOLECULAR INTERACTIONS REGULATING SERPIN FUNCTIONDaniel Lawrence; Fiscal Year: 2001..Structurally, PAI-1 provides an excellent example of the general serpins ability to adopt multiple conformation states that include active, latent, oxidized and noninhibitory substrate ..
- C1 INHIBITOR GENE AND HEREDITARY ANGIONEUROTIC EDEMAAlvin Davis; Fiscal Year: 2007..To compare and contrast the structure of C1INH with other serpins, recombinant truncated C1INH will be crystallized...
- BIOCHEMISTRY OF PROPHENOL OXIDASE ACTIVATING PROTEINASEHaobo Jiang; Fiscal Year: 2003..The inhibition reactions of the proteinase by M. sexta serpins and Kunitz-type trypsin inhibitors will be investigated to understand the physiological regulation of the enzyme...
- GENE REGULATION OF MAMMALIAN DNA VIRUSESRichard Moyer; Fiscal Year: 1999..proteins will be screened genetically by means of the yeast two-hybrid system, and biochemically by use of tagged serpins. The results of these assays will be linked to an extensive analysis of the behavior of knockout and site- ..
- GENE REGULATION OF MAMMALIAN DNA VIRUSESRichard Moyer; Fiscal Year: 2005..They focus here on poxvirus-encoded proteinase inhibitors (serpins). Orthopoxviruses, including cowpox virus (CPV), encode three serpins: SPI-1, SPI-2/crmA and SPI-3...
- Mechanisms of Hemostatic Protease Inhibition by SerpinsIngrid Verhamme; Fiscal Year: 2009The long-term goal is to define the molecular mechanisms of thrombin (T) inhibition by the serpins, heparin cofactor II (HCII) and plasminogen activator inhibitor-1 (PAI-1), implicated in arterial thrombosis...
- Mechanisms of Hemostatic Protease Inhibition by SerpinsIngrid Verhamme; Fiscal Year: 2007The long-term goal is to define the molecular mechanisms of thrombin (T) inhibition by the serpins, heparin cofactor II (HCII) and plasminogen activator inhibitor-1 (PAI-1), implicated in arterial thrombosis...
- Mechanisms of Hemostatic Protease Inhibition by SerpinsIngrid M Verhamme; Fiscal Year: 2010The long-term goal is to define the molecular mechanisms of thrombin (T) inhibition by the serpins, heparin cofactor II (HCII) and plasminogen activator inhibitor-1 (PAI-1), implicated in arterial thrombosis...
- Tyrosine Sulfation and Chemokine Receptor FunctionKevin Moore; Fiscal Year: 2006..of proteins are known to be tyrosine sulfated in man, including certain adhesion molecules, coagulation factors, serpins, extracellular matrix proteins, and hormones and some of these require sulfation for optimal function...
- Serpin Regulation of Coagulation ProteasesALIREZA REZAIE; Fiscal Year: 2009The activity of coagulation proteases is regulated primarily by the serine protease inhibitors (serpins) in plasma. Antithrombin (AT) is a major serpin that regulates the activity of proteases of both intrinsic and extrinsic pathways...
- Serpin Regulation of Coagulation ProteasesAlireza R Rezaie; Fiscal Year: 2010The activity of coagulation proteases is regulated primarily by the serine protease inhibitors (serpins) in plasma. Antithrombin (AT) is a major serpin that regulates the activity of proteases of both intrinsic and extrinsic pathways...
- Poxvirus proteins involved in virion binding, membrane fusion, & entry into cellsRichard Moyer; Fiscal Year: 2007..We focus here on poxvirus- encoded serine proteinase inhibitors (serpins). Orthopoxviruses, including cowpox virus (CPV), encode three serpins: SPI-1, SPl-2/crmA and SPI-3...
- PROTEINASE SYSTEMS IN INSECT HEMOLYMPHMichael Kanost; Fiscal Year: 2003..4. Analyze the regulation of plasma proteinases by M. sexta serine protease inhibitors (serpins).
- PROTEINASE SYSTEMS IN INSECT HEMOLYMPHMichael Kanost; Fiscal Year: 2006..4. Analyze the regulation of plasma proteinases by M. sexta serine protease inhibitors (serpins).
- Intracellular Serpin Regulation of Intestinal Cell NecrosisGARY SILVERMAN; Fiscal Year: 2009..Extensive searches within the largest family of peptidase inhibitors, the serpins (e.g., antithrombin and 11-antitrypsin), failed to yield candidate regulatory genes...
- MOLECULAR MECHANISM OF THROMBIN INHIBITIONScott Cooper; Fiscal Year: 2003..The objective of this research is to better understand the different mechanisms by which the serpins antithrombin (AT) and protein C inhibitor (PCI) inhibit free thrombin and thrombin bound to thrombomodulin (TM)...
- REGULATION OF EXTRACELLULAR PROTEOLYSIS BY SERPINSDANIEL KNAUER; Fiscal Year: 2004..This places PN1, FXIa, APP and the LRP in a common biochemical pathway that may be directly involved in Alzheimer's disease pathology. ..
- Anti-inflammatory Serpin(AAT and Elafin) Gene Transfers*Sihong Song; Fiscal Year: 2003..Lines of evidence suggest that serpins, namely AAT and elafin, may play important roles in protecting islets from autoimmunity and alloimmnunity...
- STRUCTURE AND FUNCTION OF HEPARIN COFACTOR IIDOUGLAS TOLLEFSEN; Fiscal Year: 2000..In the second Specific Aim, peptides which mimic the reactive site loop present in all serpins will be evaluated with respect to their ability to influence HCII inhibitory functions...
- SERINE PROTEASE INHIBITORS & MECHANISMS OF INFLAMATIONHarvey Rubin; Fiscal Year: 2004..We are studying a family of high molecular weight plasma and cellular proteins, the serpins--serine protease inhibitors, some of which have evolved the remarkable property of inhibiting these proteases ..
