Genomes and Genes
Summary: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
- Inouye K, Tomoishi M, Yasumoto M, Miyake Y, Kojima K, Tsuzuki S, et al. Roles of CUB and LDL receptor class A domain repeats of a transmembrane serine protease matriptase in its zymogen activation. J Biochem. 2013;153:51-61 pubmed publisher..Our findings provide new insights into the roles of these non-catalytic domains in the generation of active matriptase. ..
- Seidah N, Poirier S, Denis M, Parker R, Miao B, Mapelli C, et al. Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation. PLoS ONE. 2012;7:e41865 pubmed publisher..Finally, we identified an AnxA2 coding polymorphism, V98L, that correlates with lower circulating levels of PCSK9 thereby extending our results on the physiological role of AnxA2 in humans. ..
- Jacob M, Chang L, Pure E. Fibroblast activation protein in remodeling tissues. Curr Mol Med. 2012;12:1220-43 pubmed..Finally, we discuss the potential risks and therapeutic benefits of targeting FAP and FAP-expressing cells, as well as approaches to do so. ..
- Hansen G, Hilgenfeld R. Architecture and regulation of HtrA-family proteins involved in protein quality control and stress response. Cell Mol Life Sci. 2013;70:761-75 pubmed publisher..The HtrA protein family represents a remarkable example of how structural and functional diversity is attained from the assembly of simple molecular building blocks. ..
- Koren M, Scott R, Kim J, Knusel B, Liu T, Lei L, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet. 2012;380:1995-2006 pubmed publisher..The results of our study support the further assessment of AMG 145 in long-term studies with larger and more diverse populations including patients with documented statin intolerance. Amgen. ..
- Qu X, Randhawa G, Friedman C, O Hara Larrivee S, Kroeger K, Dumpit R, et al. A novel four-color fluorescence in situ hybridization assay for the detection of TMPRSS2 and ERG rearrangements in prostate cancer. Cancer Genet. 2013;206:1-11 pubmed publisher..Analysis using the four-color FISH assay provides sensitive detection of TMPRSS2 and ERG gene rearrangements in prostate cancer. ..
- Benjannet S, Hamelin J, Chretien M, Seidah N. Loss- and gain-of-function PCSK9 variants: cleavage specificity, dominant negative effects, and low density lipoprotein receptor (LDLR) degradation. J Biol Chem. 2012;287:33745-55 pubmed..All Asp(374) mutations resulted in similar gain-of-function activity on the LDLR except that D374E was as active as native PCSK9, D374G was relatively less active, and D374N and D374P were completely inactive. ..
- Hisanaga A, Morishita S, Suzuki K, Sasaki K, Koie M, Kohno T, et al. A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) cleaves Reelin in an isoform-dependent manner. FEBS Lett. 2012;586:3349-53 pubmed publisher..Among ADAMTS-4 isoforms, p50 cleaves the N-t site only, while p75 cleaves both sites. This is the first report identifying a protease that can specifically cleave Reelin. ..
- Valenti L, Rametta R, Dongiovanni P, Motta B, Canavesi E, Pelusi S, et al. The A736V TMPRSS6 polymorphism influences hepatic iron overload in nonalcoholic fatty liver disease. PLoS ONE. 2012;7:e48804 pubmed publisher..59, 0.39-0.88). The p.Ala736Val TMPRSS6 variant influences secondary hepatic iron accumulation in patients with NAFLD. ..
- Chretien M. My road to Damascus: how I converted to the prohormone theory and the proprotein convertases. Biochem Cell Biol. 2012;90:750-68 pubmed publisher..The discovery helped me to complete the loop: "From the bedside to the bench and back to the bedside." ..
- Liang B, Wu M, Bu Y, Zhao A, Xie F. Prognostic value of TMPRSS4 expression in patients with breast cancer. Med Oncol. 2013;30:497 pubmed publisher..Based on our results, we propose TMPRSS4 as a putative biological marker for breast cancer and as an indicator of poor prognosis. ..
- Sharotri V, Collier D, Olson D, Zhou R, Snyder P. Regulation of epithelial sodium channel trafficking by proprotein convertase subtilisin/kexin type 9 (PCSK9). J Biol Chem. 2012;287:19266-74 pubmed publisher..By reducing ENaC channel number, PCSK9 could modulate epithelial Na(+) absorption, a major contributor to blood pressure control. ..
- Giugliano R, Desai N, Kohli P, Rogers W, Somaratne R, Huang F, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase . Lancet. 2012;380:2007-17 pubmed publisher..The results suggest that PCSK9 inhibition could be a new model in lipid management. Inhibition of PCSK9 warrants assessment in phase 3 clinical trials. Amgen. ..
- Raju R, Unnikrishnan M, Rubin D, Krishnamoorthy V, Kandror O, Akopian T, et al. Mycobacterium tuberculosis ClpP1 and ClpP2 function together in protein degradation and are required for viability in vitro and during infection. PLoS Pathog. 2012;8:e1002511 pubmed publisher..These observations suggest that the Clp protease plays an unusual and essential role in Mtb and may serve as an ideal target for antimycobacterial therapy. ..
- Wang Y, Huang Y, Hobbs H, Cohen J. Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR. J Lipid Res. 2012;53:1932-43 pubmed publisher..Finally, the PCSK9-LDLR complex appears not to be transported by the canonical ESCRT pathway. ..
- Tapia Pastrana G, Chávez Dueñas L, Lanz Mendoza H, Teter K, Navarro Garcia F. VirK is a periplasmic protein required for efficient secretion of plasmid-encoded toxin from enteroaggregative Escherichia coli. Infect Immun. 2012;80:2276-85 pubmed publisher..Thus, VirK facilitates the secretion of the AT Pet by maintaining the passenger domain in a conformation that both avoids periplasmic proteolysis and facilitates ?-domain insertion into the outer membrane. ..
- Kim S, Sauer R. Cage assembly of DegP protease is not required for substrate-dependent regulation of proteolytic activity or high-temperature cell survival. Proc Natl Acad Sci U S A. 2012;109:7263-8 pubmed publisher..We discuss potential coupling mechanisms and why cage formation may have evolved if it is not required for DegP proteolysis. ..
- Hagstrom S, Ying G, Pauer G, Sturgill Short G, Huang J, Callanan D, et al. Pharmacogenetics for genes associated with age-related macular degeneration in the Comparison of AMD Treatments Trials (CATT). Ophthalmology. 2013;120:593-599 pubmed publisher..Although specific alleles for CFH, ARMS2, HTRA1, and C3 may predict the development of AMD, they did not predict response to anti-vascular endothelial growth factor therapy. ..
- Roth E, McKenney J, Hanotin C, Asset G, Stein E. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med. 2012;367:1891-900 pubmed publisher..Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT01288469.). ..
- Schönegge A, Villa E, Förster F, Hegerl R, Peters J, Baumeister W, et al. The structure of human tripeptidyl peptidase II as determined by a hybrid approach. Structure. 2012;20:593-603 pubmed publisher..Analyses of the resulting hybrid structure of the HsTPPII holocomplex provide new insights into the mechanism of maturation and activation. ..
- Valenti L, Fracanzani A, Rametta R, Fraquelli M, Soverini G, Pelusi S, et al. Effect of the A736V TMPRSS6 polymorphism on the penetrance and clinical expression of hereditary hemochromatosis. J Hepatol. 2012;57:1319-25 pubmed publisher..05). The p.A736V TMPRSS6 polymorphism is likely a modifier of HH expression. Additional studies are warranted to validate these findings in other cohorts and test their potential relevance for the clinical management of HH patients. ..
- Ai D, Chen C, Han S, Ganda A, Murphy A, Haeusler R, et al. Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice. J Clin Invest. 2012;122:1262-70 pubmed publisher..We therefore suggest that PCSK9 inhibition could be an effective way to reduce the adverse side effect of increased LDL levels that is observed in transplant patients taking rapamycin as immunosuppressive therapy. ..
- Kysenius K, Muggalla P, Mätlik K, Arumae U, Huttunen H. PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling. Cell Mol Life Sci. 2012;69:1903-16 pubmed publisher..We conclude that PCSK9 potentiates neuronal apoptosis via modulation of ApoER2 levels and related anti-apoptotic signaling pathways. ..
- Folsom T, Fatemi S. The involvement of Reelin in neurodevelopmental disorders. Neuropharmacology. 2013;68:122-35 pubmed publisher..Increasing Reelin expression through pharmacological therapies may help ameliorate symptoms resulting from Reelin deficits. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. ..
- Liang X, Lai T, Liu D, Fan A, Chen L, Tam P, et al. Differentiation of exudative age-related macular degeneration and polypoidal choroidal vasculopathy in the ARMS2/HTRA1 locus. Invest Ophthalmol Vis Sci. 2012;53:3175-82 pubmed publisher..Different effect sizes indicate the existence of additional genetic and environmental factors affecting them to different extents. ..
- Herring A, Donath A, Steiner K, Widera M, Hamzehian S, Kanakis D, et al. Reelin depletion is an early phenomenon of Alzheimer's pathology. J Alzheimers Dis. 2012;30:963-79 pubmed publisher..This early event hints at a possible causative role of RELN decline in the precipitation of AD pathology and supports RELN's potential as a pre-clinical marker for AD. ..
- Eigenbrot C, Ultsch M, Lipari M, Moran P, Lin S, Ganesan R, et al. Structural and functional analysis of HtrA1 and its subdomains. Structure. 2012;20:1040-50 pubmed publisher..Our structures of the unliganded HtrA1 active site suggest two-state equilibrium and a "conformational selection" model, in which substrate binds to the active conformer. ..
- Gebhard L, Kaufman S, Gamarnik A. Novel ATP-independent RNA annealing activity of the dengue virus NS3 helicase. PLoS ONE. 2012;7:e36244 pubmed publisher..We propose that, according to the ATP availability, NS3 could function regulating the folding or unfolding of viral RNA structures. ..
- Nitsche C, Behnam M, Steuer C, Klein C. Retro peptide-hybrids as selective inhibitors of the Dengue virus NS2B-NS3 protease. Antiviral Res. 2012;94:72-9 pubmed publisher..The results of a competition assay with the known inhibitor aprotinin indicate that the N-terminal arylcyanoacrylamide residue of this compound class binds near the catalytic center of the enzyme. ..
- Arenas J, Nijland R, Rodriguez F, Bosma T, Tommassen J. Involvement of three meningococcal surface-exposed proteins, the heparin-binding protein NhbA, the ?-peptide of IgA protease and the autotransporter protease NalP, in initiation of biofilm formation. Mol Microbiol. 2013;87:254-68 pubmed publisher..We conclude that NhbA and the ?-peptide of IgA protease are implicated in biofilm formation by binding eDNA and that NalP is an important regulator of this process through the proteolysis of these surface-exposed proteins. ..
- Stein E, Mellis S, Yancopoulos G, Stahl N, Logan D, Smith W, et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012;366:1108-18 pubmed publisher..Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT01026597, NCT01074372, and NCT01161082.). ..
- Lipari M, Li W, Moran P, Kong Beltran M, Sai T, Lai J, et al. Furin-cleaved proprotein convertase subtilisin/kexin type 9 (PCSK9) is active and modulates low density lipoprotein receptor and serum cholesterol levels. J Biol Chem. 2012;287:43482-91 pubmed publisher..Therapeutic anti-PCSK9 approaches that neutralize both forms should be the most effective in preserving LDL receptors and in lowering plasma LDL cholesterol. ..
- Sekine K, Kawauchi T, Kubo K, Honda T, Herz J, Hattori M, et al. Reelin controls neuronal positioning by promoting cell-matrix adhesion via inside-out activation of integrin ?5?1. Neuron. 2012;76:353-69 pubmed publisher..These data indicate that Reelin-dependent activation of neuronal adhesion to the extracellular matrix is crucial for the eventual birth-date-dependent layering of the neocortex. ..
- Abedi F, Wickremasinghe S, Richardson A, Islam A, Guymer R, Baird P. Genetic influences on the outcome of anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration. Ophthalmology. 2013;120:1641-8 pubmed publisher..The authors have no proprietary or commercial interest in any materials discussed in this article. ..
- Canuel M, Sun X, Asselin M, Paramithiotis E, Prat A, Seidah N. Proprotein convertase subtilisin/kexin type 9 (PCSK9) can mediate degradation of the low density lipoprotein receptor-related protein 1 (LRP-1). PLoS ONE. 2013;8:e64145 pubmed publisher..Identification of PCSK9 targets should allow a better understanding of the consequences of PCSK9 inhibition for lowering LDLc and tumor metastasis. ..
- Tiaden A, Breiden M, Mirsaidi A, Weber F, Bahrenberg G, Glanz S, et al. Human serine protease HTRA1 positively regulates osteogenesis of human bone marrow-derived mesenchymal stem cells and mineralization of differentiating bone-forming cells through the modulation of extracellular matrix protein. Stem Cells. 2012;30:2271-82 pubmed publisher..These data therefore implicate HTRA1 as having a central role in osteogenesis through modification of proteins within the extracellular matrix. ..
- Raal F, Scott R, Somaratne R, Bridges I, Li G, Wasserman S, et al. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inh. Circulation. 2012;126:2408-17 pubmed publisher..URL: http://www.clinicaltrials.gov. Unique identifier: NCT01375751. ..
- Saavedra Y, Day R, Seidah N. The M2 module of the Cys-His-rich domain (CHRD) of PCSK9 protein is needed for the extracellular low-density lipoprotein receptor (LDLR) degradation pathway. J Biol Chem. 2012;287:43492-501 pubmed publisher..The results showed no activity of any secreted deletant compared with PCSK9. Thus, although M2 is dispensable for secretion, its presence is required for the extracellular activity of PCSK9 on cell surface LDLR. ..
- Zhang Y, Zhou L, Kong Beltran M, Li W, Moran P, Wang J, et al. Calcium-independent inhibition of PCSK9 by affinity-improved variants of the LDL receptor EGF(A) domain. J Mol Biol. 2012;422:685-696 pubmed publisher..This approach may provide a new paradigm for the use of diversity libraries to improve affinities of members of the Ca(2+)-binding EGF domain subfamily. ..
- Matrisciano F, Tueting P, Dalal I, Kadriu B, Grayson D, Davis J, et al. Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice. Neuropharmacology. 2013;68:184-94 pubmed publisher..Thus, PRS mice may be a valid model for the investigation of new drugs for schizophrenia treatment targeting DNA methylation. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. ..
- McKenney J, Koren M, Kereiakes D, Hanotin C, Ferrand A, Stein E. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol. 2012;59:2344-53 pubmed publisher..Efficacy and Safety Evaluation of SAR236553 [REGN727] in Patients With Primary Hypercholesterolemia and LDL-cholesterol on Stable Atorvastatin Therapy; NCT01288443). ..
- Patsis C, Yiotakis I, Scorilas A. Diagnostic and prognostic significance of human kallikrein 11 (KLK11) mRNA expression levels in patients with laryngeal cancer. Clin Biochem. 2012;45:623-30 pubmed publisher..26, P=0.042). Our data recommend KLK11 mRNA expression as a novel and independent biomarker in laryngeal cancer for diagnostic and prognostic purposes. ..
- Burri D, Pasqual G, Rochat C, Seidah N, Pasquato A, Kunz S. Molecular characterization of the processing of arenavirus envelope glycoprotein precursors by subtilisin kexin isozyme-1/site-1 protease. J Virol. 2012;86:4935-46 pubmed publisher..In sum, our study reveals important differences in the SKI-1/S1P processing of viral and cellular substrates...
- Kosenko T, Golder M, Leblond G, Weng W, Lagace T. Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation. J Biol Chem. 2013;288:8279-88 pubmed publisher..These data suggest that association of PCSK9 with LDL particles in plasma lowers the ability of PCSK9 to bind to cell surface LDLRs, thereby blunting PCSK9-mediated LDLR degradation. ..
- Seidah N. Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors in the treatment of hypercholesterolemia and other pathologies. Curr Pharm Des. 2013;19:3161-72 pubmed..This opens the door to novel applications of PCSK9 inhibitors/silencers in cancer/metastasis. ..
- Tennstaedt A, Pöpsel S, Truebestein L, Hauske P, Brockmann A, Schmidt N, et al. Human high temperature requirement serine protease A1 (HTRA1) degrades tau protein aggregates. J Biol Chem. 2012;287:20931-41 pubmed publisher..These data suggest that HTRA1 is performing regulated proteolysis during protein quality control, the implications of which are discussed. ..