Research Topics
Genomes and Genes
| N G SeidahSummaryAffiliation: Clinical Research Institute of Montreal Country: Canada Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Proprotein Convertase Subtilisin Kexin 9 (PCSK9) Inhibitors in the Treatment of Hypercholesterolemia and other PathologiesNabil G Seidah
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal IRCM, affiliated with the University of Montreal, 110 Pine Avenue West Montreal, Québec H2W1R7, Canada
Curr Pharm Des 19:3161-72. 2013..This opens the door to novel applications of PCSK9 inhibitors/silencers in cancer/metastasis...
The biology and therapeutic targeting of the proprotein convertasesNabil G Seidah
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal affiliated to University of Montreal, 110 Pine Ave West, Montreal, Quebec H2W 1R7, Canada
Nat Rev Drug Discov 11:367-83. 2012....
Chloroquine is a potent inhibitor of SARS coronavirus infection and spreadMartin J Vincent
Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA
Virol J 2:69. 2005..Severe acute respiratory syndrome (SARS) is caused by a newly discovered coronavirus (SARS-CoV). No effective prophylactic or post-exposure therapy is currently available...
The proprotein convertase PC5/6 is protective against intestinal tumorigenesis: in vivo mouse modelXiaowei Sun
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, affiliated to the University of Montreal, Montreal, Quebec, Canada
Mol Cancer 8:73. 2009..Aside from the role of furin in salivary gland tumorigenesis, no other in vivo genetic model of PC-knockout was reported in relation to cancer development...
The activation and physiological functions of the proprotein convertasesNabil G Seidah
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada
Int J Biochem Cell Biol 40:1111-25. 2008..These data provide evidence that an inhibitor of PCSK9-LDLR interaction is a viable target for the development of a novel cholesterol lowering drug in conjunction with the classical statins...
Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptidesN G Seidah
Laboratories of Biochemical and Molecular Neuroendocrinology and the Protein Engineering Network of Centres of Excellence, Clinical Research Institute of Montreal, Canada
Brain Res 848:45-62. 1999....
Precursor convertases in the secretory pathway, cytosol and extracellular milieuNabil G Seidah
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, Canada H2W 1R7
Essays Biochem 38:79-94. 2002..NRDc could represent the equivalent of the PCs in the cytosol or the extracellular space...
Unexpected similarity between the cytosolic West Nile virus NS3 and the secretory furin-like serine proteinasesNabil G Seidah
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal, QC, H2W 1R7, Canada
Biochem J 393:e1-3. 2006..Structural modelling based on Dengue virus NS3 provided a possible rationale for the observed cleavage specificity of West Nile virus NS3...
The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiationNabil G Seidah
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, H2W 1R7 Canada
Proc Natl Acad Sci U S A 100:928-33. 2003..5 telencephalon cells led to enhanced recruitment of undifferentiated neural progenitor cells into the neuronal lineage, suggesting that NARC-1 is implicated in the differentiation of cortical neurons...
The proprotein convertases are potential targets in the treatment of dyslipidemiaNabil G Seidah
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal, Quebec, H2W 1R7, Canada
J Mol Med (Berl) 85:685-96. 2007..Specific inhibitors/modulators of the other PCs should find novel therapeutic applications in the control of PC-regulated pathologies...
PCSK9 as a therapeutic target of dyslipidemiaNabil G Seidah
Clinical Research Institute of Montreal, Laboratory of Biochemical Neuroendocrinology, 110 Pine Ave West, Montreal, QC, H2W 1R7 Canada
Expert Opin Ther Targets 13:19-28. 2009..Its gene is associated with the development of familial hypercholesterolemia. mRNA silencing or inhibition of PCSK9-induced degradation of LDLR may be used to treat this disease...
What lies ahead for the proprotein convertases?Nabil G Seidah
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Canada
Ann N Y Acad Sci 1220:149-61. 2011..In vivo studies demonstrated that PCs play major roles in health and disease states...
Cloning and primary sequence of a mouse candidate prohormone convertase PC1 homologous to PC2, Furin, and Kex2: distinct chromosomal localization and messenger RNA distribution in brain and pituitary compared to PC2N G Seidah
J A DeSève Laboratories of Biochemical, Clinical Research Institute of Montreal, Quebec, Canada
Mol Endocrinol 5:111-22. 1991..The genes coding for mPC1 and mPC2 map to the murine chromosomes 13 (band 13c) and 2 (2F3-2H2 region), respectively...
The prosegments of furin and PC7 as potent inhibitors of proprotein convertases. In vitro and ex vivo assessment of their efficacy and selectivityM Zhong
Laboratory of Biochemical, Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec H2W 1R7
J Biol Chem 274:33913-20. 1999..Thus, we have demonstrated for the first time that PC prosegments, expressed ex vivo as independent domains, can act in trans to inhibit precursor maturation by intracellular PCs...
Comparative biosynthesis, covalent post-translational modifications and efficiency of prosegment cleavage of the prohormone convertases PC1 and PC2: glycosylation, sulphation and identification of the intracellular site of prosegment cleavage of PC1 and PS Benjannet
J A DeSève Laboratory of Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
Biochem J 294:735-43. 1993..In order to test the possibility that zymogen processing is performed by furin, we co-expressed this convertase with either pro-PC1 or pro-PC2. The data demonstrated the inability of furin to cleave either proenzyme...
cDNA sequence of two distinct pituitary proteins homologous to Kex2 and furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinasesN G Seidah
J A DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
DNA Cell Biol 9:415-24. 1990..8 kb) demonstrated tissue and cellular specificity of expression, only within endocrine and neuroendocrine cells. These data suggest that mPC1 and mPC2 represent prime candidates for tissue-specific pro-hormone converting proteinases...
The isoforms of proprotein convertase PC5 are sorted to different subcellular compartmentsI De Bie
J A De Sève Laboraotry of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, QC, Canada
J Cell Biol 135:1261-75. 1996..Thus, a single PC5 gene generates COOH-terminally modified isoforms with different sorting signals directing these proteins to distinct subcellular localization, thereby allowing them to process their appropriate substrates...
Mammalian subtilisin/kexin isozyme SKI-1: A widely expressed proprotein convertase with a unique cleavage specificity and cellular localizationN G Seidah
Laboratory of Biochemical, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, Canada H2W 1R7
Proc Natl Acad Sci U S A 96:1321-6. 1999..In vitro studies suggest that SKI-1 is a Ca2+-dependent serine proteinase exhibiting a wide pH optimum for cleavage of pro-brain-derived neurotrophic factor...
Cellular processing of the nerve growth factor precursor by the mammalian pro-protein convertasesN G Seidah
J A DeSève Laboratories of Biochemical and Molecular Neuroendocrinology, Clinical Research Institute of Montreal, University of Montreal, Canada
Biochem J 314:951-60. 1996..This comparative study shows that the three candidate mammalian subtilisin/kexin-like convertases identified process proNGF into NGF and that the nature of the final processed products is dependent on the intracellular environment...
Mouse plasma kallikrein: cDNA structure, enzyme characterization, and comparison of protein and mRNA levels among speciesN G Seidah
J A DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
DNA Cell Biol 9:737-48. 1990..The regulation of the mRNA stability and/or turnover rate of PK may possibly be affected by its 5' end in a species-dependent manner...
cDNA structure of the mouse and rat subtilisin/kexin-like PC5: a candidate proprotein convertase expressed in endocrine and nonendocrine cellsJ Lusson
J A DeSève Laboratorie of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, PQ, Canada
Proc Natl Acad Sci U S A 90:6691-5. 1993..In situ hybridization of rat brain sections demonstrated a unique distribution of PC5 compared to PC1, PC2, and furin...
Structure-function studies on the biosynthesis and bioactivity of the precursor convertase PC2 and the formation of the PC2/7B2 complexS Benjannet
J A de Sève Laboratory of Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Canada
FEBS Lett 362:151-5. 1995....
Enzymic characterization in vitro of recombinant proprotein convertase PC4A Basak
Molecular Neuroendocrinology Laboratory, Clinical Research Institute of Montreal, Montreal, Que, Canada
Biochem J 343:29-37. 1999..PC4A was also inhibited by transition-metal ions (Cu(2+)>Hg(2+)>Zn(2+) Ni(2+)>Co(2+)), as well as by small peptide semicarbazones (SCs), such as Arg-Lys-Lys-Arg-SC (K(i) 0.75 microM) and Arg-Ser-Lys-Arg-SC (K(i) 11.4 microM)...
Structure of the gene for the testis-specific proprotein convertase 4 and of its alternate messenger RNA isoformsM Mbikay
Laboratoires de Neuroendocrinologie, Universite de Montreal, Quebec, Canada
Genomics 20:231-7. 1994..The multiple forms of PC4 mRNA can all be explained by alternate splicing of primary transcripts of a single gene...
Identification and localization of 7B2 protein in human, porcine, and rat thyroid gland and in human medullary carcinomaM Marcinkiewicz
J A de Sève Laboratories of Biochemical and Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
Endocrinology 123:866-73. 1988..Results suggest that 7B2 may play a role in endocrine function, possibly as a secretory substance, and may be a histochemical marker in addition to calcitonin for medullary carcinoma...
Gene organization of the mouse pro-hormone and pro-protein convertase PC1N Ftouhi
J A DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
DNA Cell Biol 13:395-407. 1994..Using a 3' end probe specifically hybridizing with the 5-kb mRNA, we show that in the mouse pituitary neurointermediate lobe the 3-kb form is negatively regulated by dopamine, while the 5-kb form is not...
Comparative functional role of PC7 and furin in the processing of the HIV envelope glycoprotein gp160E Decroly
J A DeSève Laboratory of Biochemical Neuroendocrinology, University of Montreal, QC, Canada
FEBS Lett 405:68-72. 1997..The data demonstrate that PC7 can cleave specifically and in a cell-type specific manner gp160 into gp120gp41, suggesting that both furin and PC7 are so far the major PC-like candidate gp160 convertase in T4 lymphocytes...
Prosomatostatin is proteolytically processed at the amino terminal segment by subtilase SKI-1R Mouchantaf
Fraser Laboratories, Department of Medicine, Room M3-15, Royal Victoria Hospital, McGill University, 687 Pine Avenue West, Montreal, Quebec, Canada H3A 1A1
Regul Pept 120:133-40. 2004..Mutagenesis studies showed that efficient processing of PSST to PSST[1-10] required the RXRXXL motif. However, this NH2-terminal cleavage was not a prerequisite for the formation of SST-14 and SST-28...
The family of subtilisin/kexin like pro-protein and pro-hormone convertases: divergent or shared functionsN G Seidah
JA DeSève Laboratories of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Que, Canada
Biochimie 76:197-209. 1994..Although the genetic organization of the convertase genes is very similar, they exhibit unique promoter sequences and only furin and PACE4 genes are localized on the same chromosome...
The LIM homeobox protein mLIM3/Lhx3 induces expression of the prolactin gene by a Pit-1/GHF-1-independent pathway in corticotroph AtT20 cellsS E Girardin
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Que, Canada
FEBS Lett 431:333-8. 1998..We conclude that mLIM3 may play a key role in inducing PRL gene expression in lactotrophs by binding to a conserved motif close to a Pit-1/GHF-1 site within the proximal PRL promoter...
Functional analysis of human PACE4-A and PACE4-C isoforms: identification of a new PACE4-CS isoformM Zhong
J A DeSève Laboratories of Biochemical Neuroendocrinology Clinical Research Institute of Montreal, University of Montreal, QC, Canada
FEBS Lett 396:31-6. 1996..Microsequencing of the intracellular PACE4-CS protein in two cell lines revealed that it is proPACE4-CS with an N-terminal trimming reminiscent of the action of a dipeptidylpeptidase recognizing the motifs X-Ala and X-Pro...
Comparative cellular processing of the human immunodeficiency virus (HIV-1) envelope glycoprotein gp160 by the mammalian subtilisin/kexin-like convertasesF Vollenweider
J A DeSève Laboratories of Biochemical and Molecular Neuroendocrinology, Montreal, Quebec, Canada
Biochem J 314:521-32. 1996..Finally, the co-expression of the [Arg355, Arg358]-alpha-1-antitrypsin Portland variant was shown to potently inhibit the processing of both gp160 and gp120 by these convertases...
Molecular cloning and biochemical characterization of a new mouse testis soluble-zinc-metallopeptidase of the neprilysin familyG Ghaddar
Departement de Biochimie, Faculte de Medecine, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, Quebec, Canada H3C 3J7
Biochem J 347:419-29. 2000..This distribution of NL1 mRNA suggests that it could be involved in sperm formation or other processes related to fertility...
cDNA structure, tissue distribution, and chromosomal localization of rat PC7, a novel mammalian proprotein convertase closest to yeast kexin-like proteinasesN G Seidah
Clinical Research Institute of Montreal, Canada
Proc Natl Acad Sci U S A 93:3388-93. 1996..The gene for PC7 (Pcsk7) was mapped to mouse chromosome 9 by linkage analysis of an interspecific backcross DNA panel...
Chromosomal assignments of the genes for neuroendocrine convertase PC1 (NEC1) to human 5q15-21, neuroendocrine convertase PC2 (NEC2) to human 20p11.1-11.2, and furin (mouse 7[D1-E2] region)N G Seidah
J A DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
Genomics 11:103-7. 1991..Furthermore, the identification of the NEC1 locus on human chromosome 5 and mouse chromosome 13 suggests a conservation of synthenic regions between these regions of the human and mouse genomes...
Chromogranin B (secretogranin I), a putative precursor of two novel pituitary peptides through processing at paired basic residuesS Benjannet
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
FEBS Lett 224:142-8. 1987..These data are thus in favor of a putative role of chromogranins as precursors to potentially bioactive peptides...
Ontogeny of the prohormone convertases PC1 and PC2 in the mouse hypophysis and their colocalization with corticotropin and alpha-melanotropinM Marcinkiewicz
J A DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
Proc Natl Acad Sci U S A 90:4922-6. 1993..It is expected that beta-endorphin processing will follow that of alpha MSH...
Prohormone convertases in mouse submandibular gland: co-localization of furin and nerve growth factorH Farhadi
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Quebec, Canada
J Histochem Cytochem 45:795-804. 1997..These data, taken together with those from previous studies, suggest that furin is a candidate processing enzyme for NGF in mouse submandibular glands...
The neuroendocrine precursor 7B2 is a sulfated protein proteolytically processed by a ubiquitous furin-like convertaseL Paquet
Laboratory of Structure and Metabolism of Neuropeptides, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada
J Biol Chem 269:19279-85. 1994..These results demonstrate that pro7B2 is first processed by a furin-like enzyme within the trans-Golgi network into a 23-kDa form that is then sequestered into secretory granules...
pH-induced conformational transitions of a molten-globule-like state of the inhibitory prodomain of furin: implications for zymogen activationS Bhattacharjya
Biomolecular Nuclear Magnetic Resonance Laboratory, Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec H4P 2R2, Canada
Protein Sci 10:934-42. 2001....
7B2 is a specific intracellular binding protein of the prohormone convertase PC2S Benjannet
J A DeSève Laboratories of Molecular, Clinical Research Institute of Montreal, Quebec, Canada
J Neurochem 64:2303-11. 1995..Coexpression of 7B2 and PC2, although resulting in an elevation of the level of pro-PC2, did not eliminate the processing of pro-PC2 to PC2.(ABSTRACT TRUNCATED AT 250 WORDS)..
The cDNA sequence of the human pro-hormone and pro-protein convertase PC1N G Seidah
J A DeSève Laboratory of Biochemical, Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
DNA Cell Biol 11:283-9. 1992..2 kb and the presence of smaller transcripts in some tissues. The major site of production of hPC1 seems to be the pituitary and brain, although detection was also possible in pancreas and heart...
The cDNA structure of rat plasma kallikreinN G Seidah
Laboratory of Biochemical Neuronendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
DNA 8:563-74. 1989....
Proprotein conversion is determined by a multiplicity of factors including convertase processing, substrate specificity, and intracellular environment. Cell type-specific processing of human prorenin by the convertase PC1S Benjannet
J A DeSève Laboratory of Molecular Neuroendocrinology, University of Montreal, Quebec, Canada
J Biol Chem 267:11417-23. 1992..Our data demonstrate that propeptide removal from these enzymes, possibly leading to their activation, is not the only criterion which governs precursor processing...
Biosynthesis and enzymatic characterization of human SKI-1/S1P and the processing of its inhibitory prosegmentB B Touré
Laboratory of Biochemical, Protein Engineering Network of Centres of Excellence, Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec H2W 1R7
J Biol Chem 275:2349-58. 2000..Finally, we demonstrate that, in vitro, recombinant prosegments of SKI-1 inhibit its activity with apparent inhibitor constants of 100-200 nM...
Electron microscopic immunocytochemical evidence for the involvement of the convertases PC1 and PC2 in the processing of proinsulin in pancreatic beta-cellsD Malide
Department of Anatomy, Universite de Montreal, Quebec, Canada
J Histochem Cytochem 43:11-9. 1995..Co-expression of PC1 and PC2 with proinsulin in islet beta-cells indicates that these proteases are actively involved, probably in a sequential manner, in the conversion of proinsulin into insulin...
Histidine-rich human salivary peptides are inhibitors of proprotein convertases furin and PC7 but act as substrates for PC1A Basak
Laboratory of Structure and Metabolism of Neuropeptides, Clinical Research Institute of Montreal, Quebec, Canada
J Pept Res 49:596-603. 1997..When tested against rPC7, H3 exhibited almost identical inhibition profile with a measured Ki of 2.4 microM. The partial sequence identity of H3 to the inhibitory pro-peptide of furin and PC7 provides a rationale for our observation...
Comparative analysis of expression of the proprotein convertases furin, PACE4, PC1 and PC2 in human lung tumoursM Mbikay
Institut de Recherches Cliniques de Montreal, Universite de Montreal, Quebec, Canada
Br J Cancer 75:1509-14. 1997....
Processing of prodynorphin by the prohormone convertase PC1 results in high molecular weight intermediate forms. Cleavage at a single arginine residueA Dupuy
J A DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
FEBS Lett 337:60-5. 1994..Additionally, PC1 cleaves proDyn at a single arginine residue to yield an 8 kDa product and the C-peptide. This demonstrates that PC1 cleaves proDyn at single and pairs of basic residues...
Heterologous processing of rat prosomatostatin to somatostatin-14 by PC2: requirement for secretory cell but not the secretion granuleA S Galanopoulou
Fraser Laboratories, McGill University Department of Medicine, Royal Victoria Hospital, Montreal, Quebec, Canada
Biochem J 311:111-8. 1995..The activity of PC2 requires the milieu of the secretory cell but not the secretory granule...
Processed forms of neuroendocrine proteins 7B2 and secretogranin II are found in porcine pituitary extractsC Lazure
J A De Sève Laboratory of Molecular, Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada, University of Montreal
Int J Pept Protein Res 38:392-400. 1991....
Inhibitory activity and structural characterization of a C-terminal peptide fragment derived from the prosegment of the proprotein convertase PC7S Bhattacharjya
Biomolecular NMR Laboratory, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montreal, Quebec, Canada H4P 2R2
Biochemistry 39:2868-77. 2000..We surmise that such a structure-function correlation for an inhibitory peptide could lead to the design and discovery of molecules mimicking the specific interactions of the PC prosegments for their cognate proteases...
Pilocarpine-induced seizures are accompanied by a transient elevation in the messenger RNA expression of the prohormone convertase PC1 in rat hippocampus: comparison with nerve growth factor and brain-derived neurotrophic factor expressionM Marcinkiewicz
J A DeSève Laboratory of Molecular Neuroendocrinology, University ofMontreal, Quebec, Canada
Neuroscience 76:425-39. 1997..Our findings suggest the involvement of PC1 in the processing of precursor proteins during seizure activity...
Secretory protein 7B2 is associated with pancreatic hormones within normal islets and some experimentally induced tumorsS Benjannet
J A de Sève Laboratories of Molecular and Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
Endocrinology 123:874-84. 1988..In addition, IR-7B2 could be detected immunocytochemically in three of seven tumors produced in the rat by streptozotocin-nicotinamide treatment...
Molecular cloning and expression of the ovine testicular follicle stimulating hormone receptorT A Yarney
Reproduction Research Laboratory, Clinical Research Institute of Montreal, Quebec, Canada
Mol Cell Endocrinol 93:219-26. 1993..Chemically deglycosylated oFSH (DG-oFSH) was inactive in these cells but it effectively blocked the action of native hormone.(ABSTRACT TRUNCATED AT 250 WORDS)..
The mouse homeoprotein mLIM-3 is expressed early in cells derived from the neuroepithelium and persists in adult pituitaryN G Seidah
J A DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada
DNA Cell Biol 13:1163-80. 1994..These data suggest a potential role for mLIM-3 in the transcriptional regulation of certain genes during morphogenesis and/or maintenance of the differentiated state of the pituitary, motor neurons, and pineal gland...
Developmental expression of the prohormone convertases PC1 and PC2 in mouse pancreatic isletsM Marcinkiewicz
J A DeSève Laboratories of Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
Endocrinology 135:1651-60. 1994....
Processing of alpha4 integrin by the proprotein convertases: histidine at position P6 regulates cleavageEric Bergeron
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, Canada, H2W 1R7
Biochem J 373:475-84. 2003..In conclusion, although the accepted furin processing motif is Arg-Xaa-(Lys/Arg)-Arg downward arrow, our data further extend it to include a regulatory histidine residue at P6 in precursors that lack a basic residue at P4...
The regulated cell surface zymogen activation of the proprotein convertase PC5A directs the processing of its secretory substratesGaetan Mayer
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 283:2373-84. 2008..A similar mechanism may also apply to the convertase PACE4, thereby extending our knowledge of the molecular details of the zymogen activation and functions of these heparan sulfate proteoglycan-bound convertases...
The production by alternate splicing of two mRNAs differing by one codon could be an intrinsic property of neuroendocrine protein 7B2 gene expression in manL Paquet
Laboratoires J A de Sève de Neuroendocrinologie Moléculaire et Biochimique, Institut de Recherches Cliniques de Montreal, Quebec, Canada
Biochem Biophys Res Commun 174:156-62. 1991....
Two-dimensional immunoblotting analysis and immunocytochemical localization of the secretory polypeptide 7B2 in adrenal medullaM Marcinkiewicz
J A de Sève Laboratories of Molecular and Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Que, Canada
Neurosci Lett 95:81-7. 1988..These data establish that in chromaffin granules 7B2 represents a minor component of the acidic proteins which include the chromogranins A and B, secretogranin II and the enkephalin-containing peptides...
Heparin enhances the furin cleavage of HIV-1 gp160 peptidesA Pasquato
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada H2W 1R7
FEBS Lett 581:5807-13. 2007..Our data support the hypothesis of a direct binding of heparin with site1 and site2, allowing selective exposure/accessibility of the REKR sequence, which is only then optimally cleaved by furin...
Processing specificity and biosynthesis of the Drosophila melanogaster convertases dfurin1, dfurin1-CRR, dfurin1-X, and dfurin2I De Bie
J A DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
J Biol Chem 270:1020-8. 1995..The conclusions drawn from the results of this study may well be applicable to the mammalian convertases PC4, PACE4, and PC5, which also display C-terminal sequence heterogeneity...
Post-translational processing of beta-secretase (beta-amyloid-converting enzyme) and its ectodomain shedding. The pro- and transmembrane/cytosolic domains affect its cellular activity and amyloid-beta productionS Benjannet
Biochemical Neuroendocrinology, , Montreal, Quebec H2W 1R7, Canada
J Biol Chem 276:10879-87. 2001..These findings suggest that the shedding of BACE may play a role in the amyloidogenic processing of betaAPP...
Prohormone convertase PC5 is a candidate processing enzyme for prorenin in the human adrenal cortexC Mercure
Laboratory of Molecular Biochemistry of Hypertension, Clinical Research Institute of Montreal, Quebec, Canada
Hypertension 28:840-6. 1996..Human PC5 was colocalized with renin by immunohistochemistry in the zona glomerulosa of the adrenal gland, suggesting that it could participate in the activation of a local renin-angiotensin system in the human adrenal cortex...
The proteolytic processing of pro-platelet-derived growth factor-A at RRKR(86) by members of the proprotein convertase family is functionally correlated to platelet-derived growth factor-A-induced functions and tumorigenicityGeraldine Siegfried
Laboratory of Biochemical Neuroendocrinology Clinical Research Institute of Montreal, Montreal, Quebec, H2W 1R7, Canada
Cancer Res 63:1458-63. 2003..Chinese hamster ovary cells overexpressing pro-PDGF-A (ARKA(86)) failed to induce tumors in nude mice. Thus, PC-directed inhibitors might represent new agents for therapy in neoplasia induced by PDGF-A...
Coordinated expression of beta-amyloid precursor protein and the putative beta-secretase BACE and alpha-secretase ADAM10 in mouse and human brainM Marcinkiewicz
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada
J Neurochem 75:2133-43. 2000..Our data provide cytochemical evidence supporting the role of ADAM10 and BACE as authentic alpha- and beta-secretases...
Gene structure and chromosomal localization of plasma kallikreinG Beaubien
J A DeSève Laboratories of Biochemical and Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
Biochemistry 30:1628-35. 1991....
Testicular expression of PC4 in the rat: molecular diversity of a novel germ cell-specific Kex2/subtilisin-like proprotein convertaseN G Seidah
J A DeSève Laboratories of Biochemical, Clinical Research Institute of Montreal, Quebec, Canada
Mol Endocrinol 6:1559-70. 1992..The stage-specific expression of PC4 in testis indicates its potential role in the developmental maturation of germ cells and that this convertase may play a specific physiological function in reproduction...
Eukaryotic protein processing: endoproteolysis of precursor proteinsN G Seidah
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, QC, Canada
Curr Opin Biotechnol 8:602-7. 1997....
The secretory proprotein convertases furin, PC5, and PC7 activate VEGF-C to induce tumorigenesisGeraldine Siegfried
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada
J Clin Invest 111:1723-32. 2003..Our findings demonstrate the processing of proVEGF-C by PCs and highlight the potential use of PC inhibitors as agents for inhibiting malignancies induced by VEGF-C...
NH2-terminal fragment of rat pro-atrial natriuretic factor in the circulation: identification, radioimmunoassay and half-lifeG Thibault
Clinical Research Institute of Montreal, Quebec, Canada
Peptides 9:47-53. 1988..The exponential decay was analyzed by a two-compartment model in which the fast and slow components had a half-life of 2.5 +/- 0.3 and 54.8 +/- 3.9 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)..
Proprotein convertase subtilisin/kexin type 9 (PCSK9): hepatocyte-specific low-density lipoprotein receptor degradation and critical role in mouse liver regenerationAhmed Zaid
Laboratorie of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, affiliated to the University of Montreal, Montreal, Quebec, Canada
Hepatology 48:646-54. 2008..CONCLUSION: Although PCSK9 is a target for controlling hypercholesterolemia, our data indicate that upon hepatic damage, patients lacking PCSK9 could be at risk...
The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinasesNadia Nour
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
Mol Biol Cell 16:5215-26. 2005..In conclusion, the CRD of PC5A and PACE4 functions as a cell surface anchor favoring the processing of their cognate surface-anchored substrates, including endothelial lipase...
Development of protein-based inhibitors of the proprotein of convertase SKI-1/S1P: processing of SREBP-2, ATF6, and a viral glycoproteinPhilomena Pullikotil
Laboratories of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 279:17338-47. 2004..Finally, these inhibitors were also shown to affect the processing and stability of the Crimean-Congo hemorrhagic fever virus glycoprotein...
The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2Steve Poirier
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 283:2363-72. 2008..Thus, this study demonstrates a more general effect of PCSK9 on the degradation of the LDLR family that emphasizes its major role in cholesterol and lipid homeostasis as well as brain development...
NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterolSuzanne Benjannet
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 279:48865-75. 2004..In conclusion, NARC-1 seems to affect both the level of LDLR and that of circulating apoB-containing lipoproteins in an LDLR-dependent and -independent fashion...
Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemiaGeneviève Dubuc
Laboratory of Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Quebec, Canada
Arterioscler Thromb Vasc Biol 24:1454-9. 2004..The 2 other known genes implicated in ADH encode the low-density lipoprotein receptor and apolipoprotein B. As an approach toward the elucidation of the physiological role(s) of NARC-1, we studied its transcriptional regulation...
Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: evidence for an intracellular routeSteve Poirier
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 284:28856-64. 2009..Therefore, targeting either pathway, or both, would be an effective method to reduce PCSK9 activity in the treatment of hypercholesterolemia and coronary heart disease...
Deletion of the gene encoding proprotein convertase 5/6 causes early embryonic lethality in the mouseRachid Essalmani
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada
Mol Cell Biol 26:354-61. 2006..5 and 7.5. These data demonstrate that Pcsk5 is an essential gene...
Proprotein convertases in tumor progression and malignancy: novel targets in cancer therapyAbdel Majid Khatib
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada
Am J Pathol 160:1921-35. 2002..Thus, PC inhibitors may constitute new promising agents for the treatment of multiple tumors and/or in adjuvant therapy to prevent recurrence...
The proprotein convertase SKI-1/S1P. In vitro analysis of Lassa virus glycoprotein-derived substrates and ex vivo validation of irreversible peptide inhibitorsAntonella Pasquato
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 281:23471-81. 2006....
Circulating proprotein convertase subtilisin/kexin 9 (PCSK9) regulates VLDLR protein and triglyceride accumulation in visceral adipose tissueAnna Roubtsova
Laboratory of Biochemical Neuroendocrinology, University of Montreal, Montreal, Quebec, Canada
Arterioscler Thromb Vasc Biol 31:785-91. 2011..Herein, we investigated the role of PCSK9 in adipose tissue metabolism...
The influence of PCSK9 polymorphisms on serum low-density lipoprotein cholesterol and risk of atherosclerosisJean Davignon
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal IRCM, 110 Pine Avenue West, Montreal, QC, H2W 1R7, Canada
Curr Atheroscler Rep 12:308-15. 2010..Which one will be clinically applicable will depend on long-term effects, cost, and ease of administration...
Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levelsGaetan Mayer
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 283:31791-801. 2008..The identification of the minimal inhibitory sequence of AnxA2 should pave the way toward the development of PCSK9 inhibitory lead molecules for the treatment of hypercholesterolemia...
The proprotein convertases and their implication in sterol and/or lipid metabolismNabil G Seidah
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal H2W 1R7, QC, Canada
Biol Chem 387:871-7. 2006..Finally, PCSK9 downregulates the protein levels of the LDLR by enhancement of its intracellular metabolic pathway in subcellular acidic compartments...
The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLRNasha Nassoury
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7
Traffic 8:718-32. 2007..Mutations that affect this transport can lead to hyper- or hypocholesterolemia...
Biosynthesis and cellular trafficking of the convertase SKI-1/S1P: ectodomain shedding requires SKI-1 activityAram Elagoz
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 277:11265-75. 2002..In conclusion, multiple domains ensuring optimal functional characteristics control SKI-1 activity and cellular trafficking...
Implication of the proprotein convertase NARC-1/PCSK9 in the development of the nervous systemSteve Poirier
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada
J Neurochem 98:838-50. 2006..These data support a novel role for NARC-1/PCSK9 in CNS development, distinct from that in cholesterogenic organs such as liver...
Structure-function analysis of the prosegment of the proprotein convertase PC5ANadia Nour
Laboratories of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 278:2886-95. 2003..In conclusion, cleavages of the prosegment of PC5A at both Arg(116) and Arg(84) are required for PC5A cellular activity, and ppPC5 is a very potent but modestly selective cellular inhibitor of PC5A...
The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modificationsSuzanne Benjannet
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 281:30561-72. 2006..The latter may reduce the lifetime of this proteinase and its ability to degrade the cell-surface LDL receptor, thereby regulating the levels of circulating LDL cholesterol...
Beta-amyloid protein converting enzyme 1 and brain-specific type II membrane protein BRI3: binding partners processed by furinLouise Wickham
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada
J Neurochem 92:93-102. 2005..Thus, furin efficiently processes both pro-BACE1 and its novel interacting protein pro-BRI3...
Implication of proprotein convertases in the processing and spread of severe acute respiratory syndrome coronavirusEric Bergeron
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Que, Canada H2W 1R7
Biochem Biophys Res Commun 326:554-63. 2005..Taken together, our data indicate that furin or PC-mediated processing plays a critical role in SARS-CoV spread and cytopathicity, and inhibitors of the PCs represent potential therapeutic anti-SARS-CoV agents...
The metalloendopeptidase nardilysin (NRDc) is potently inhibited by heparin-binding epidermal growth factor-like growth factor (HB-EGF)Véronique Hospital
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
Biochem J 367:229-38. 2002..We conclude that the DAC is thus a key regulatory element for the two distinct functions that NRDc fulfills, i.e. as an HB-EGF modulator and a peptidase...
Regulation of the proprotein convertase subtilisin/kexin type 9 in intestinal epithelial cellsFrançois Leblond
Department of Nutrition, Clinical Research Institute of Montreal, Montreal, Quebec, Canada, H3T 1C5
Am J Physiol Gastrointest Liver Physiol 296:G805-15. 2009..Furthermore, unconjugated and conjugated BA exhibited different effects on PCSK9 and LDLr. Altogether, these data indicate that intestinal PCSK9 is highly modulated by sterols and emphasize the distinct effects of BA species...
Altered processing of the neurotensin/neuromedin N precursor in PC2 knock down mice: a biochemical and immunohistochemical studyPierre Villeneuve
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
J Neurochem 82:783-93. 2002..However, there was no change in the maturation of pro-NT/NN in the brain of mice in which the PC1 gene had been partially inactivated, implying that complete PC1 knock down may be required for loss of function...
In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrateRachid Essalmani
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, Canada
Proc Natl Acad Sci U S A 105:5750-5. 2008..This work identifies Gdf11 as a likely in vivo specific substrate of PC5/6 and opens the way to the identification of other key substrates of this convertase...
PC1/3, PC2 and PC5/6A are targeted to dense core secretory granules by a common mechanismJimmy D Dikeakos
Laboratory of Molecular Biochemistry of Hypertension, Institut de recherches cliniques de Montreal IRCM, QC, Canada
FEBS J 274:4094-102. 2007..Analysis of the predicted structures formed by these three granule-sorting helices shows a correlation between their granule-sorting efficiency and the clustering of hydrophobic amino acids in their granule-targeting helices...
Evidence for proprotein convertase activity in the endoplasmic reticulum/early GolgiAlexandre Salvas
Biochemical Neuroendocrinology Laboratory, Clinical Research Institute of Montreal, QC, Canada
FEBS Lett 579:5621-5. 2005..This suggests that the convertases could cleave some substrates within the ER, possibly by displacing the inhibitory prosegment associated with them...
The proprotein convertase SKI-1/S1P: alternate translation and subcellular localizationPhilomena Pullikotil
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada
J Biol Chem 282:27402-13. 2007..Deletion studies showed that the transmembrane domain of SKI-1 determines its trafficking. Finally, rSt-1 and rSt-2 seem to affect the processing of ATF6 by SKI-1, but cellular stress does not regulate the production of St-2...
Neurotrophin-4, alone or heterodimerized with brain-derived neurotrophic factor, is sorted to the constitutive secretory pathwayAndrew P Hibbert
Centre for Neuronal Survival, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada
J Biol Chem 278:48129-36. 2003..In contrast, heterodimers of NT-3 and BDNF have been shown to be released through the regulated secretory pathway. Thus, NT-4, alone or when co-expressed with BDNF, is processed within and secreted by the constitutive secretory pathway...
Research Grants
- Proprotein Processing, Trafficking and Secretion Gordon ConferenceNabil Seidah; Fiscal Year: 2006..The integration of protease systems that are required both for normal physiology and human disease will be relevant to our understanding of the molecular bases of diabetes, cancer, Alzheimer's and drug addiction. ..
