Research Topics
Genomes and Genes
| Sylvain MelocheSummaryCountry: Canada Publications
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Publications
The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transitionS Meloche
Departments of Pharmacology and Molecular Biology, Institut de Recherche en Immunologie et Cancérologie, Universite de Montreal, Montreal, Quebec, Canada
Oncogene 26:3227-39. 2007..In this review, we discuss the mechanisms by which activated ERK1/ERK2 regulate growth and cell cycle progression of mammalian somatic cells. We also highlight the findings obtained from gene disruption studies...- Erk2 signaling and early embryo stem cell self-renewalSylvain Meloche
Institut de recherche en immunovirologie et cancérologie, Universite de Montreal, Montreal, Quebec Canada
Cell Cycle 3:241-3. 2004..Thus, signaling by the ERK1/2 MAP kinase pathway appears to be critical for the regulation of self-renewal and propagation of early embryo stem cell populations... - Phosphorylation of IRF-3 on Ser 339 generates a hyperactive form of IRF-3 through regulation of dimerization and CBP associationJean François Clément
Faculte de Pharmacie, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec, Canada
J Virol 82:3984-96. 2008..Importantly, our study establishes a molecular link between the role of serine 339 in IRF-3 homodimerization, CBP association, and its destabilization... - Activation loop phosphorylation of the atypical MAP kinases ERK3 and ERK4 is required for binding, activation and cytoplasmic relocalization of MK5Paul Déléris
Institut de Recherche en Immunologie et Cancérologie, Montreal, Quebec, Canada
J Cell Physiol 217:778-88. 2008..Our results demonstrate the importance of activation loop phosphorylation in the regulation of ERK3/ERK4 function and highlight differences in the regulation of atypical MAP kinases as compared to classical family members... - Phosphorylation of Ser72 does not regulate the ubiquitin ligase activity and subcellular localization of Skp2Christel Boutonnet
Institut de Recherche en Immunologie et Cancérologie, Universite de Montreal, Montreal, QC, Canada
Cell Cycle 9:975-9. 2010..We show here that phosphorylation of Ser72 does not control Skp2 binding to Skp1 and Cul1, has no influence on SCF(Skp2) ubiquitin ligase activity, and does not affect the subcellular localization of Skp2 in a panel of cell lines... - Genetic demonstration of a redundant role of extracellular signal-regulated kinase 1 (ERK1) and ERK2 mitogen-activated protein kinases in promoting fibroblast proliferationLaure Voisin
Institut de Recherche en Immunologie et Cancérologie, Universite de Montreal, P O Box 6128, Station Centre Ville, Montreal, Quebec H3C 3J7, Canada
Mol Cell Biol 30:2918-32. 2010..Together, our findings provide compelling genetic evidence for a redundant role of ERK1 and ERK2 in promoting cell proliferation... - N-Terminal ubiquitination of extracellular signal-regulated kinase 3 and p21 directs their degradation by the proteasomePhilippe Coulombe
Institut de recherche en immunovirologie et cancérologie, Department of Molecular Biology, Universite de Montreal, Quebec, Canada
Mol Cell Biol 24:6140-50. 2004..Our results suggests that N-terminal ubiquitination is a more prevalent modification than originally recognized... - Sef downregulation by Ras causes MEK1/2 to become aberrantly nuclear localized leading to polyploidy and neoplastic transformationStéphanie Duhamel
Program of Molecular Biology, Institut de Recherche en Immunologie et Cancérologie, Universite de Montreal, Montreal, Quebec, Canada
Cancer Res 72:626-35. 2012..Taken together, our findings indicate that Ras-induced downregulation of Sef is an early oncogenic event that contributes to genetic instability and tumor progression by sustaining nuclear ERK1/2 signaling... - Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling pathwayPaul Déléris
Institut de Recherche en Immunologie et Cancérologie, Universite de Montreal, Montreal, Quebec H3C 3J7, Canada
J Biol Chem 286:6470-8. 2011..Our results reveal that group I PAKs act as upstream activators of ERK3 and ERK4 and unravel a novel PAK-ERK3/ERK4-MK5 signaling pathway... - p107 inhibits G1 to S phase progression by down-regulating expression of the F-box protein Skp2Geneviève Rodier
Institut de recherche en immunovirologie et cancérologie, Universite de Montreal, Montreal, Quebec H3C 3J7, Canada
J Cell Biol 168:55-66. 2005..We propose that p107, in addition to its interaction with E2F, inhibits cell proliferation through the control of Skp2 expression and the resulting stabilization of p27... - An essential function of the mitogen-activated protein kinase Erk2 in mouse trophoblast developmentMarc K Saba-El-Leil
Institut de Recherches Cliniques de Montréal and Department of Pharmacology, Universite de Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7
EMBO Rep 4:964-8. 2003..The inability of Erk1 to compensate for Erk2 function suggests a specific function for Erk2 in normal trophoblast development in the mouse, probably in regulating the proliferation of polar trophectoderm cells... - Activation of MEK1 or MEK2 isoform is sufficient to fully transform intestinal epithelial cells and induce the formation of metastatic tumorsLaure Voisin
Institut de Recherche en Immunologie et Cancérologie, Montreal, Quebec, Canada
BMC Cancer 8:337. 2008..However, the exact contribution of MEK1 and MEK2 to the pathogenesis of colorectal cancer remains to be established... - Phosphorylation of Skp2 regulated by CDK2 and Cdc14B protects it from degradation by APC(Cdh1) in G1 phaseGeneviève Rodier
Institut de Recherche en Immunologie et Cancérologie, Universite de Montreal, Montreal, Quebec, Canada
EMBO J 27:679-91. 2008..Thus, our results reveal that reversible phosphorylation plays a key role in the timing of Skp2 expression in the cell cycle... - Nuclear export of ERK3 by a CRM1-dependent mechanism regulates its inhibitory action on cell cycle progressionCatherine Julien
Institut de Recherches Cliniques de Montreal, Universite de Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 278:42615-24. 2003..Our results suggest that nucleocytoplasmic shuttling of ERK3 is required for its negative regulatory effect on cell cycle progression... - Loss of Erk3 function in mice leads to intrauterine growth restriction, pulmonary immaturity, and neonatal lethalitySonia Klinger
Institut de Recherche en Immunologie et Cancérologie and Departments of Pharmacology and Molecular Biology, Universite de Montreal, Montreal, Quebec, Canada
Proc Natl Acad Sci U S A 106:16710-5. 2009..Our findings reveal a critical role for Erk3 in the establishment of fetal growth potential and pulmonary function in the mouse... - Sustained in vitro trigger of self-renewal divisions in Hoxb4hiPbx1(10) hematopoietic stem cellsSonia Cellot
Laboratory of Molecular Genetics of Stem Cells, Institute for Research in Immunology and Cancer IRIC, Montreal, QC, Canada
Exp Hematol 35:802-16. 2007..We thus put forward this strategy as an efficient in vitro HSC expansion tool, enabling a further step into the avenue of self-renewal molecular effectors... - C-terminal domain phosphorylation of ERK3 controlled by Cdk1 and Cdc14 regulates its stability in mitosisPierre Luc Tanguay
Institut de Recherche en Immunologie et Cancérologie, Universite de Montreal, Montreal, Quebec, Canada H3C 3J7
Biochem J 428:103-11. 2010..The results of the present study identify a novel regulatory mechanism of ERK3 that operates in a cell-cycle-dependent manner... - Involvement of the IkappaB kinase (IKK)-related kinases tank-binding kinase 1/IKKi and cullin-based ubiquitin ligases in IFN regulatory factor-3 degradationAnnie Bibeau-Poirier
Faculty of Pharmacy, University of Montreal, Montreal, Canada
J Immunol 177:5059-67. 2006.... - EN2 is a candidate oncogene in human breast cancerNicole L Martin
Laboratory of Molecular Genetics of Hematopoietic Stem Cells, Institut de Recherche en Immunologie et Cancérologie, CP 6128, Succursale Centre Ville, Montreal, Quebec, Canada H3C 3J7
Oncogene 24:6890-901. 2005..RNA interference studies suggest that EN2 expression is required for the maintenance of the transformed phenotype of a human breast tumor cell line... - The eIF4E RNA regulon promotes the Akt signaling pathwayBiljana Culjkovic
Institute for Research in Immunology and Cancer, Universite de Montreal, Montreal, Québec H4M 1J6, Canada
J Cell Biol 181:51-63. 2008..In summary, eIF4E coordinately regulates gene expression to potentiate Akt activation, an activity required for apoptotic rescue... - Targeted inactivation of Mapk4 in mice reveals specific nonredundant functions of Erk3/Erk4 subfamily mitogen-activated protein kinasesJustine Rousseau
Institut de Recherche en Immunologie et Cancérologie, Universite de Montreal, Montreal, Quebec, Canada
Mol Cell Biol 30:5752-63. 2010..Our analysis indicates that the MAP kinase Erk4 is dispensable for mouse embryonic development and reveals that Erk3 and Erk4 have acquired specialized functions through evolutionary diversification... - Liver fibrosis protects mice from acute hepatocellular injuryEric Bourbonnais
Laboratoire d Hépatologie Cellulaire du Centre de Recherche du CHUM Hôpital Saint Luc, Montreal, Quebec, Canada
Gastroenterology 142:130-139.e4. 2012.... - Artifactual sulfation of silver-stained proteins: implications for the assignment of phosphorylation and sulfation sitesMarlene Gharib
Institute of Research in Immunology and Cancer IRIC, Universite de Montreal, Montreal, Quebec, Canada
Mol Cell Proteomics 8:506-18. 2009..02%, which is typically used for silver staining. The significance of this artifact is discussed in the broader context of sulfation and phosphorylation site identification from in vivo and in vitro experiments... - ProteoConnections: a bioinformatics platform to facilitate proteome and phosphoproteome analysesMathieu Courcelles
IRIC, Institute of Research in Immunology and Cancer, Universite de Montreal, Montreal, Canada Department of Biochemistry, Universite de Montreal, Montreal, Canada
Proteomics 11:2654-71. 2011.... - Cyclic AMP induces morphological changes of vascular smooth muscle cells by inhibiting a Rac-dependent signaling pathwayStephane Pelletier
Institut de recherche en immunovirologie et cancérologie, Universite de Montreal, Montreal, Quebec, Canada
J Cell Physiol 204:412-22. 2005..We further show that activated Rac1 containing the F37A effector loop substitution fails to rescue the cAMP phenotype. Our results suggest that cAMP modulates the morphology of VSMCs by inhibiting a Rac-dependent signaling pathway... - Chromosome mapping of the human genes encoding the MAP kinase kinase MEK1 (MAP2K1) to 15q21 and MEK2 (MAP2K2) to 7q32S Meloche
Research Centre, Centre hospitalier de l Université de Montréal and Department of Pharmacology, University of Montreal, Quebec, Canada
Cytogenet Cell Genet 88:249-52. 2000..We also present evidence for the presence of a MEK1 pseudogene on chromosome 8p21. The MEK2 gene (MAP2K2) was mapped to chromosome 7q32 by fluorescence in situ hybridization and YAC clone analysis... - p38 MAP kinase pathway regulates angiotensin II-induced contraction of rat vascular smooth muscleS Meloche
Centre de Recherche, Centre Hospitalier de l Universite de Montreal, and Department of Pharmacology, University of Montreal, Montreal, Quebec, Canada H2W 1T8
Am J Physiol Heart Circ Physiol 279:H741-51. 2000..These results suggest that the p38 MAP kinase pathway selectively modulates the vasoconstrictor action of ANG II in vascular smooth muscle... - From basic research to clinical development of MEK1/2 inhibitors for cancer therapyChristophe Frémin
Institut de Recherche en Immunologie et Cancérologie and Department of Pharmacology, Universite de Montreal, Montreal, Quebec H3C 3J7, Canada
J Hematol Oncol 3:8. 2010..We then present the current state of clinical evaluation of MEK1/2 inhibitors in cancer and discuss challenges ahead... - Dual regulation of MMP-2 expression by the type 1 insulin-like growth factor receptor: the phosphatidylinositol 3-kinase/Akt and Raf/ERK pathways transmit opposing signalsDonglei Zhang
Department of Surgery, McGill University Health Center, The Royal Victoria Hospital, Room H6 25, 687 Pine Avenue West, Montreal, Quebec, Canada H3A 1A1
J Biol Chem 279:19683-90. 2004..The outcome of IGF-IR (the receptor for IGF-I) activation may ultimately depend on factors, such as ligand bioavailability, that can shift the balance preferentially toward one pathway or the other... - Phosphorylation of the MAPKKK regulator Ste50p in Saccharomyces cerevisiae: a casein kinase I phosphorylation site is required for proper mating functionCunle Wu
Genetics Group, Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec, Canada H4P 2R2
Eukaryot Cell 2:949-61. 2003..However, this phosphorylation does not seem to have a detectable role in modulating the high-osmolarity glycerol synthesis pathway... - The Rb-family protein p107 inhibits translation by a PDK1-dependent mechanismConstantin Makris
Institut de Recherches Cliniques de Montréal and Department of Pharmacology, University of Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada
Oncogene 21:7891-6. 2002..Overexpression of PDK1 restores the defect in translation elicited by p107. These results suggest that p107 restricts cell growth by interfering with the phosphoinositide 3-kinase (PI3K) signaling pathway... - Cloning and characterization of mouse extracellular-signal-regulated protein kinase 3 as a unique gene product of 100 kDaB Turgeon
Research Centre, Centre Hospitalier de l Universite de Montreal, Hotel Dieu Campus, 3850 Saint Urbain Street, Montreal, Quebec, Canada
Biochem J 346:169-75. 2000..Finally, we provide several lines of evidence to support the existence of a unique Erk3 gene product of 100 kDa in mammalian cells... - Chromosomal localization of the mouse genes encoding the ERK1 and ERK2 isoforms of MAP kinasesM K Saba-El-Leil
Centre de Recherche, , Quebec, Canada
Mamm Genome 8:141-2. 1997 - The IKK-related kinases: from innate immunity to oncogenesisJean François Clément
Faculte de Pharmacie, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec, Canada H3C 3J7
Cell Res 18:889-99. 2008..This review will therefore summarize and discuss the role of TBK1 and IKKi in cellular transformation and oncogenesis by focusing on their regulation and substrate specificity... - ER stress affects processing of MHC class I-associated peptidesDiana P Granados
Department of Medicine, Institute for Research in Immunology and Cancer, Universite de Montreal, Montreal, Canada
BMC Immunol 10:10. 2009..We therefore asked whether and how the UPR impinges on MHC I-peptide presentation... - Atypical mitogen-activated protein kinases: structure, regulation and functionsPhillipe Coulombe
Institut de Recherche en Immunologie et Cancérologie and Department of Pharmacology, Universite de Montreal, Montreal, Quebec, Canada H3C 3J7
Biochim Biophys Acta 1773:1376-87. 2007..Atypical MAP kinases include ERK3/ERK4, NLK and ERK7. Much less is known about the regulation, substrate specificity and physiological functions of atypical MAP kinases... - Rapid turnover of extracellular signal-regulated kinase 3 by the ubiquitin-proteasome pathway defines a novel paradigm of mitogen-activated protein kinase regulation during cellular differentiationPhilippe Coulombe
Institut de Recherches Cliniques de Montreal, Universite de Montreal, Montreal, Quebec H2W 1R7, Canada
Mol Cell Biol 23:4542-58. 2003..Interestingly, we found that expression of stabilized forms of ERK3 causes G(1) arrest in NIH 3T3 cells. We propose that ERK3 biological activity is regulated by its cellular abundance through the control of protein stability... - Interpreting neonatal lethal phenotypes in mouse mutants: insights into gene function and human diseasesBenjamin Turgeon
Department of Pharmacology and Molecular Biology, Universite de Montreal, Montreal, Quebec, Canada
Physiol Rev 89:1-26. 2009..This review provides a guide for the analysis of neonatal lethal phenotypes in mutant mice that will be helpful for dissecting out the function of specific genes during mouse development... - Effects of angiotensin-converting enzyme inhibitor versus valsartan on cellular signaling events in heart transplantMichel White
Department of Medicine, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada
Ann Pharmacother 43:831-9. 2009..The changes in the cardiac angiotensin system signaling pathways in the human heart in response to ACE inhibitors versus ARBs have been incompletely studied... - Primary structure, expression and chromosomal locus of a human homolog of rat ERK3S Meloche
Centre de Recherche, Hotel Dieu de Montreal, Quebec, Canada
Oncogene 13:1575-9. 1996..This information should prove valuable in designing studies to define the cellular function of the ERK3 protein kinase... - p27 cytoplasmic localization is regulated by phosphorylation on Ser10 and is not a prerequisite for its proteolysisG Rodier
Institut de Recherches Cliniques de Montreal, University of Montreal, Montreal, Quebec, Canada H2W 1R7
EMBO J 20:6672-82. 2001..This cytoplasmic localization may serve to decrease the abundance of p27 in the nucleus below a certain threshold required for activation of cyclin-Cdk2 complexes... - Expression of angiotensin type II receptor downregulates Cdk4 synthesis and inhibits cell-cycle progressionBruno Gingras
, , 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7
Oncogene 22:2633-42. 2003..These findings suggest that the growth-inhibitory effects of the AT(2) receptor are attributable in part to its spontaneous inhibitory action on the cell cycle machinery... - Assignment of the human angiotensin II type 2 receptor gene (AGTR2) to chromosome Xq22-q23 by fluorescence in situ hybridizationC Chassagne
Centre de Recherche, , Quebec, Canada
Genomics 25:601-3. 1995 - Human immunodeficiency virus gp120 and derived peptides activate protein tyrosine kinase p56lck in human CD4 T lymphocytesC Hivroz
INSERM U132, Hopital Necker Enfants Malades, Paris, France
Eur J Immunol 23:600-7. 1993..This activation led to a specific pattern of tyrosine phosphorylation on cellular proteins that may be of significance in the biological effects of the gp120/CD4 interaction, e.g. syncytium formation and inhibition of T cell activation...