Carlos Lopez-Otin

Summary

Affiliation: Universidad de Oviedo
Country: Spain

Publications

  1. ncbi request reprint Exome sequencing identifies a novel mutation in PIK3R1 as the cause of SHORT syndrome
    Clea Bárcena
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    BMC Med Genet 15:51. 2014
  2. pmc Nuclear envelope defects cause stem cell dysfunction in premature-aging mice
    Jesus Espada
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Cell Biol 181:27-35. 2008
  3. pmc Rejuvenating somatotropic signaling: a therapeutical opportunity for premature aging?
    Alejandro P Ugalde
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Aging (Albany NY) 2:1017-22. 2010
  4. pmc The Degradome database: mammalian proteases and diseases of proteolysis
    Victor Quesada
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nucleic Acids Res 37:D239-43. 2009
  5. pmc NF-kB in premature aging
    Fernando G Osorio
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Aging (Albany NY) 4:726-7. 2012
  6. pmc The genomic landscape of chronic lymphocytic leukemia: clinical implications
    Victor Quesada
    Departamento de Bioquimica y Biologia Molecular, Universidad de Oviedo IUOPA, Oviedo, Spain
    BMC Med 11:124. 2013
  7. pmc Epigenetic repression of ROR2 has a Wnt-mediated, pro-tumourigenic role in colon cancer
    Ester Lara
    Department of Immunology and Oncology, National Center for Biotechnology, CNB CSIC, Cantoblanco, Madrid E 28049, Spain
    Mol Cancer 9:170. 2010
  8. pmc Matrix metalloproteinase-8 deficiency increases joint inflammation and bone erosion in the K/BxN serum-transfer arthritis model
    Samuel Garcia
    Research Laboratory and Rheumatology Unit, Complexo Hospitalario Universitario de Santiago de Compostela CHUS, SERGAS, Biomedical Research Institute IDIS, Travesia da Choupana s n, Santiago de Compostela, 15706 A Coruna, Spain
    Arthritis Res Ther 12:R224. 2010
  9. pmc Comparative genomic analysis of the zebra finch degradome provides new insights into evolution of proteases in birds and mammals
    Victor Quesada
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    BMC Genomics 11:220. 2010
  10. doi request reprint The regulatory crosstalk between kinases and proteases in cancer
    Carlos Lopez-Otin
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nat Rev Cancer 10:278-92. 2010

Detail Information

Publications84

  1. ncbi request reprint Exome sequencing identifies a novel mutation in PIK3R1 as the cause of SHORT syndrome
    Clea Bárcena
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    BMC Med Genet 15:51. 2014
    ..Additionally, the patients usually present a low birth weight and height, lipodystrophy, delayed bone age, hernias, low body mass index and a progeroid appearance...
  2. pmc Nuclear envelope defects cause stem cell dysfunction in premature-aging mice
    Jesus Espada
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Cell Biol 181:27-35. 2008
    ..These findings establish a link between age-related nuclear envelope defects and stem cell dysfunction...
  3. pmc Rejuvenating somatotropic signaling: a therapeutical opportunity for premature aging?
    Alejandro P Ugalde
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Aging (Albany NY) 2:1017-22. 2010
    ..Here, we summarize these observations and discuss the importance of GH/IGF-1 balance in longevity as well as its modulation as a putative therapeutic strategy for the treatment of human progeroid syndromes...
  4. pmc The Degradome database: mammalian proteases and diseases of proteolysis
    Victor Quesada
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nucleic Acids Res 37:D239-43. 2009
    ..Finally, the user can find additional information about protease structures, protease inhibitors, ancillary domains of proteases and differences between mammalian degradomes...
  5. pmc NF-kB in premature aging
    Fernando G Osorio
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Aging (Albany NY) 4:726-7. 2012
    ..Thus, experimental data confirm that NF-κB signaling is active during normal aging, its hyperactivation is associated with the development of accelerated aging and its amelioration retards the aging process...
  6. pmc The genomic landscape of chronic lymphocytic leukemia: clinical implications
    Victor Quesada
    Departamento de Bioquimica y Biologia Molecular, Universidad de Oviedo IUOPA, Oviedo, Spain
    BMC Med 11:124. 2013
    ..Herein, we review the recent advances in the definition of the genomic landscape of CLL and the ongoing research to characterize the underlying biochemical events that drive this disease...
  7. pmc Epigenetic repression of ROR2 has a Wnt-mediated, pro-tumourigenic role in colon cancer
    Ester Lara
    Department of Immunology and Oncology, National Center for Biotechnology, CNB CSIC, Cantoblanco, Madrid E 28049, Spain
    Mol Cancer 9:170. 2010
    ..Despite increasing evidence of the role of the non-canonical pathways in tumourigenesis, however, the underlying molecular mechanisms are poorly understood...
  8. pmc Matrix metalloproteinase-8 deficiency increases joint inflammation and bone erosion in the K/BxN serum-transfer arthritis model
    Samuel Garcia
    Research Laboratory and Rheumatology Unit, Complexo Hospitalario Universitario de Santiago de Compostela CHUS, SERGAS, Biomedical Research Institute IDIS, Travesia da Choupana s n, Santiago de Compostela, 15706 A Coruna, Spain
    Arthritis Res Ther 12:R224. 2010
    ..However, the role of specific MMPs in arthritis pathogenesis is largely unknown. The aim of the present study was to investigate the role of Mmp-8 (collagenase-2) in an arthritis model...
  9. pmc Comparative genomic analysis of the zebra finch degradome provides new insights into evolution of proteases in birds and mammals
    Victor Quesada
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    BMC Genomics 11:220. 2010
    ..Therefore, the sequencing of the zebra finch genome allows the comparison between the degradomes of mammals and birds and may help to understand the biological peculiarities of the zebra finch...
  10. doi request reprint The regulatory crosstalk between kinases and proteases in cancer
    Carlos Lopez-Otin
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nat Rev Cancer 10:278-92. 2010
    ..The functional consequences of this regulatory crosstalk are especially relevant in the different stages of cancer progression. What are the clinical implications derived from the fertile dialogue between kinases and proteases in cancer?..
  11. ncbi request reprint Emerging roles of proteases in tumour suppression
    Carlos Lopez-Otin
    Carlos López Otín is at the Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nat Rev Cancer 7:800-8. 2007
    ..These effects are associated with more than 30 different enzymes that belong to three distinct protease classes. What are the clinical implications of these findings?..
  12. pmc Exome sequencing and functional analysis identifies BANF1 mutation as the cause of a hereditary progeroid syndrome
    Xose S Puente
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    Am J Hum Genet 88:650-6. 2011
    ..These data demonstrate the utility of exome sequencing for identifying the cause of rare Mendelian disorders and underscore the importance of nuclear envelope alterations in human aging...
  13. ncbi request reprint Cloning, expression analysis, and structural characterization of seven novel human ADAMTSs, a family of metalloproteinases with disintegrin and thrombospondin-1 domains
    Santiago Cal
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006, Oviedo, Spain
    Gene 283:49-62. 2002
    ....
  14. pmc Nuclear lamina defects cause ATM-dependent NF-κB activation and link accelerated aging to a systemic inflammatory response
    Fernando G Osorio
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    Genes Dev 26:2311-24. 2012
    ..Our findings provide in vivo proof of principle for the feasibility of pharmacological modulation of the NF-κB pathway to slow down the progression of physiological and pathological aging...
  15. ncbi request reprint Identification and characterization of human and mouse ovastacin: a novel metalloproteinase similar to hatching enzymes from arthropods, birds, amphibians, and fish
    Victor Quesada
    Departamento de Bioquimica y Biologia Molecular and Morfologia y Biologia Celular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Biol Chem 279:26627-34. 2004
    ..On the basis of these results, we suggest that ovastacin could play in mammals a physiological function similar to that performed by hatching proteases in evolutionary distant species from arthropods to fish...
  16. pmc Aging and chronic DNA damage response activate a regulatory pathway involving miR-29 and p53
    Alejandro P Ugalde
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    EMBO J 30:2219-32. 2011
    ..Based on these results, we propose the existence of a novel regulatory circuitry involving miR-29, Ppm1d and p53, which is activated in aging and in response to DNA damage...
  17. pmc Polyserase-I, a human polyprotease with the ability to generate independent serine protease domains from a single translation product
    Santiago Cal
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Proc Natl Acad Sci U S A 100:9185-90. 2003
    ....
  18. pmc Insulin-like growth factor 1 treatment extends longevity in a mouse model of human premature aging by restoring somatotroph axis function
    Guillermo Mariño
    Departamento de Bioquímica y Biología Molecular and Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Proc Natl Acad Sci U S A 107:16268-73. 2010
    ..Our findings highlight the importance of IGF/GH balance in longevity and may be of therapeutic interest for devastating human progeroid syndromes associated with nuclear envelope abnormalities...
  19. ncbi request reprint Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation
    Ignacio Varela
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nature 437:564-8. 2005
    ....
  20. ncbi request reprint Identification and characterization of human archaemetzincin-1 and -2, two novel members of a family of metalloproteases widely distributed in Archaea
    Araceli Diaz-Perales
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Biol Chem 280:30367-75. 2005
    ..Finally, these activities were abolished by inhibitors of metalloproteases, providing further evidence that AMZs belong to this catalytic class of proteolytic enzymes...
  21. ncbi request reprint Matriptase-2, a membrane-bound mosaic serine proteinase predominantly expressed in human liver and showing degrading activity against extracellular matrix proteins
    Gloria Velasco
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Biol Chem 277:37637-46. 2002
    ....
  22. ncbi request reprint Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice
    Alberto M Pendas
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nat Genet 31:94-9. 2002
    ..These results indicate that prelamin A is a specific substrate for Zmpste24 and demonstrate the usefulness of genetic approaches for identifying the in vivo substrates of proteolytic enzymes...
  23. doi request reprint Absence or inhibition of matrix metalloproteinase-8 decreases ventilator-induced lung injury
    Guillermo M Albaiceta
    Department of Biología Funcional, Universidad de Oviedo, Instituto Universitario de Oncologia del Principado de Asturias, Oviedo, Spain
    Am J Respir Cell Mol Biol 43:555-63. 2010
    ..We conclude that MMP-8 promotes acute inflammation after ventilation with high pressures, and its short-term inhibition could be a therapeutic goal to limit VILI...
  24. pmc Matrix metalloproteinase Mmp-1a is dispensable for normal growth and fertility in mice and promotes lung cancer progression by modulating inflammatory responses
    Miriam Fanjul-Fernández
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Biol Chem 288:14647-56. 2013
    ..On the basis of these results, we propose that Mmp1a knock-out mice provide an excellent in vivo model for the functional analysis of human MMP-1 in both physiological and pathological conditions...
  25. ncbi request reprint Loss of collagenase-2 confers increased skin tumor susceptibility to male mice
    Milagros Balbin
    Departamentos de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nat Genet 35:252-7. 2003
    ..Our study identifies a paradoxical protective role for Mmp8 in cancer and provides a genetic model to evaluate the molecular basis of gender differences in cancer susceptibility...
  26. ncbi request reprint Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases
    Victor Quesada
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Spain
    Biochem Biophys Res Commun 314:54-62. 2004
    ....
  27. ncbi request reprint Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies
    Alicia R Folgueras
    Department of Biochemistry and Molecular Biology, Faculty of Medicine, University Institute of Oncology, Universidad de Oviedo, 33006 Oviedo, Spain
    Int J Dev Biol 48:411-24. 2004
    ....
  28. doi request reprint Nuclear envelope alterations generate an aging-like epigenetic pattern in mice deficient in Zmpste24 metalloprotease
    Fernando G Osorio
    Departamento de Bioquímica y Biología Molecular Unidad de Epigenética, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Aging Cell 9:947-57. 2010
    ..The identification of these altered genes may help to clarify the molecular mechanisms underlying aging and progeroid syndromes as well as to define new targets for the treatment of these dramatic diseases...
  29. pmc Diet-induced obesity and reduced skin cancer susceptibility in matrix metalloproteinase 19-deficient mice
    Alberto M Pendas
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Spain
    Mol Cell Biol 24:5304-13. 2004
    ..Based on these results, we suggest that this enzyme plays an in vivo role in some of the tissue remodeling events associated with adipogenesis, as well as in pathological processes such as tumor progression...
  30. doi request reprint Premature aging in mice activates a systemic metabolic response involving autophagy induction
    Guillermo Mariño
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Hum Mol Genet 17:2196-211. 2008
    ..However, the chronic activation of this catabolic pathway may turn an originally intended pro-survival strategy into a pro-aging mechanism and could contribute to the systemic degeneration and weakening observed in these progeroid mice...
  31. ncbi request reprint Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy
    Guillermo Mariño
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Spain
    J Biol Chem 278:3671-8. 2003
    ....
  32. doi request reprint Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis
    Alicia R Folgueras
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Spain
    Blood 112:2539-45. 2008
    ..On the basis of these findings, we conclude that matriptase-2 activity represents a novel and relevant step in hepcidin regulation and iron homeostasis...
  33. pmc A genomic analysis of rat proteases and protease inhibitors
    Xose S Puente
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Genome Res 14:609-22. 2004
    ..These comparative analyses may provide new views on the functional diversity of proteases and inhibitors and contribute to the development of innovative strategies for treating proteolysis diseases...
  34. pmc Autophagy is essential for mouse sense of balance
    Guillermo Mariño
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Clin Invest 120:2331-44. 2010
    ....
  35. ncbi request reprint Identification and characterization of ADAMTS-20 defines a novel subfamily of metalloproteinases-disintegrins with multiple thrombospondin-1 repeats and a unique GON domain
    Maria Llamazares
    Departamento de Bioquíimica y Biologíia Molecular, Facultad de Medicina, Instituto Universitario de Oncologíia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Biol Chem 278:13382-9. 2003
    ..These data suggest that this novel enzyme may play a role in the tissue remodeling process occurring in both normal and pathological conditions...
  36. ncbi request reprint Comparative genomic analysis of human and chimpanzee proteases
    Xose S Puente
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Genomics 86:638-47. 2005
    ..brucei infection. This study provides the first analysis of the chimpanzee degradome and might contribute to the understanding of the molecular bases underlying variations in host defense mechanisms between human and chimpanzee...
  37. pmc ADAMTS-12 metalloprotease is necessary for normal inflammatory response
    Angela Moncada-Pazos
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia IUOPA, Universidad de Oviedo, 33006 Oviedo, Spain
    J Biol Chem 287:39554-63. 2012
    ..On the basis of these results, we propose that ADAMTS-12 is implicated in the inflammatory response by modulating normal neutrophil apoptosis...
  38. ncbi request reprint AtFACE-2, a functional prenylated protein protease from Arabidopsis thaliana related to mammalian Ras-converting enzymes
    Juan Cadinanos
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, Campus del Christo, 33006 Oviedo, Spain
    J Biol Chem 278:42091-7. 2003
    ..These results provide evidence for the existence of a previously unsuspected plant FACE-2/Rce1 ortholog and support the evolutionary conservation of dual CAAX proteolytic systems in eukaryotes...
  39. ncbi request reprint Identification of human aminopeptidase O, a novel metalloprotease with structural similarity to aminopeptidase B and leukotriene A4 hydrolase
    Araceli Diaz-Perales
    Departamento de Bioquímica y Biología Molecular and Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Biol Chem 280:14310-7. 2005
    ..On the basis of these results we suggest that AP-O could play a role in the proteolytic processing of bioactive peptides in those tissues where it is expressed...
  40. doi request reprint Splicing-directed therapy in a new mouse model of human accelerated aging
    Fernando G Osorio
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Sci Transl Med 3:106ra107. 2011
    ....
  41. ncbi request reprint Matrix metalloproteinases and tumor progression
    José M P Freije
    Departamento de Bioquimica, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Adv Exp Med Biol 532:91-107. 2003
    ..Further studies directed to elucidate these questions will be necessary to clarify whether any of the multiple strategies of MMP inhibition may be part of future therapeutic approaches to control tumor progression...
  42. ncbi request reprint Structural and enzymatic characterization of Drosophila Dm2-MMP, a membrane-bound matrix metalloproteinase with tissue-specific expression
    Elena Llano
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Biol Chem 277:23321-9. 2002
    ....
  43. ncbi request reprint Human polyserase-2, a novel enzyme with three tandem serine protease domains in a single polypeptide chain
    Santiago Cal
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Biol Chem 280:1953-61. 2005
    ....
  44. ncbi request reprint The ADAMTS12 metalloproteinase exhibits anti-tumorigenic properties through modulation of the Ras-dependent ERK signalling pathway
    Maria Llamazares
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Asturias, Spain
    J Cell Sci 120:3544-52. 2007
    ..Overall, our data suggest that ADAMTS12 confers tumour-protective functions upon cells that produce this proteolytic enzyme...
  45. doi request reprint Cell autonomous and systemic factors in progeria development
    Fernando G Osorio
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Biochem Soc Trans 39:1710-4. 2011
    ....
  46. doi request reprint Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia
    Victor Quesada
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    Nat Genet 44:47-52. 2012
    ..The results reinforce the idea that targeting several well-known genetic pathways, including mRNA splicing, could be useful in the treatment of CLL and other malignancies...
  47. doi request reprint Functional analysis of sucrase-isomaltase mutations from chronic lymphocytic leukemia patients
    David Rodriguez
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    Hum Mol Genet 22:2273-82. 2013
    ..These results highlight SI as a relevant target for clinical evaluation in future CLL studies...
  48. pmc Identification and characterization of human polyserase-3, a novel protein with tandem serine-protease domains in the same polypeptide chain
    Santiago Cal
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    BMC Biochem 7:9. 2006
    ..The two first domains are enzymatically active. By contrast, polyserase-2 is an extracellular glycosylated protein whose three protease domains remain embedded in the same chain, and only the first domain possesses catalytic activity...
  49. pmc Comparative analysis of cancer genes in the human and chimpanzee genomes
    Xose S Puente
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    BMC Genomics 7:15. 2006
    ..To study whether genetic differences between human and chimpanzee could contribute to their distinct cancer susceptibility, we have examined in the chimpanzee genome the orthologous genes of a set of 333 human cancer genes...
  50. ncbi request reprint From immature lamin to premature aging: molecular pathways and therapeutic opportunities
    Juan Cadinanos
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    Cell Cycle 4:1732-5. 2005
    ..These strategies, some of which are based on existing drugs, might contribute to the development of effective treatments for these dramatic pathologies...
  51. pmc Loss of mitochondrial protease OMA1 alters processing of the GTPase OPA1 and causes obesity and defective thermogenesis in mice
    Pedro M Quirós
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    EMBO J 31:2117-33. 2012
    ..This study provides the first description of an unexpected role in energy metabolism for the metalloprotease OMA1 and reinforces the importance of mitochondrial quality control for normal metabolic function...
  52. doi request reprint Micromanaging aging with miRNAs: new messages from the nuclear envelope
    Alejandro P Ugalde
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    Nucleus 2:549-55. 2011
    ..Here, we discuss these recent discoveries and summarize the present evidences regarding the involvement of aging-associated miRNAs or geromiRs in senescence and longevity regulation...
  53. doi request reprint The nutraceutical flavonoid luteolin inhibits ADAMTS-4 and ADAMTS-5 aggrecanase activities
    Angela Moncada-Pazos
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, Spain
    J Mol Med (Berl) 89:611-9. 2011
    ..These results suggest that luteolin could be employed as a prototypic modifying disease-agent to create new chondroprotective compounds aimed to specifically block the unwanted aggrecanase activities in arthritic diseases...
  54. doi request reprint Accelerated ageing: from mechanism to therapy through animal models
    Fernando G Osorio
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006, Oviedo, Spain
    Transgenic Res 18:7-15. 2009
    ..We discuss here the use of this and other animal models to investigate the molecular mechanisms underlying accelerated ageing and to test strategies for its treatment...
  55. doi request reprint Reprogramming aging and progeria
    José M P Freije
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia IUOPA, Universidad de Oviedo, 33006 Oviedo, Spain Electronic address
    Curr Opin Cell Biol 24:757-64. 2012
    ..These results illustrate the reversibility of some aspects of the aging process and encourage the search for new anti-aging and anti-progeria interventions...
  56. doi request reprint Matrix metalloproteinase-8 functions as a metastasis suppressor through modulation of tumor cell adhesion and invasion
    Ana Gutierrez-Fernandez
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    Cancer Res 68:2755-63. 2008
    ..On this basis, we propose that MMP-8 is a tumor protective factor, which also has the ability to reduce the metastatic potential of malignant cells in both mice and human...
  57. ncbi request reprint Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3
    Guillermo Mariño
    Departamento de Bioquímica y Biología Molecular and Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Biol Chem 282:18573-83. 2007
    ..We also propose that this enzyme could play an in vivo role in events associated with tumor progression...
  58. ncbi request reprint Human and mouse proteases: a comparative genomic approach
    Xose S Puente
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nat Rev Genet 4:544-58. 2003
    ....
  59. doi request reprint POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia
    Andrew J Ramsay
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncología del Principado de Asturias IUOPA Universidad de Oviedo, Oviedo, Spain
    Nat Genet 45:526-30. 2013
    ..The identification of POT1 as a new frequently mutated gene in CLL may facilitate novel approaches for the clinical management of this disease...
  60. pmc Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis
    Andrew J Ramsay
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
    Haematologica 94:840-9. 2009
    ..In this review, after overviewing the membrane anchored serine proteases, in particular the TTSP family, we summarize the identification and characterization of matriptase-2 and describe its functional relevance in iron metabolism...
  61. doi request reprint Metalloproteases and the degradome
    Alejandro P Ugalde
    Departamento de Bioquimica y Biologia Molecular, Universidad de Oviedo, Oviedo, Spain
    Methods Mol Biol 622:3-29. 2010
    ....
  62. doi request reprint Collagenase-2 deficiency or inhibition impairs experimental autoimmune encephalomyelitis in mice
    Alicia R Folgueras
    Departamento de Bioquimica y Biologia Molecular, and Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, and Servicio de Anatomía Patológica, Hospital Central de Asturias, Oviedo 33006, Spain
    J Biol Chem 283:9465-74. 2008
    ..Based on these findings, we conclude that MMP-8 plays an important role in EAE development and propose that this enzyme may be a novel therapeutic target in human neuro-inflammatory diseases such as multiple sclerosis...
  63. pmc Resistance to bleomycin-induced lung fibrosis in MMP-8 deficient mice is mediated by interleukin-10
    Emilio García-Prieto
    Department of Biología Funcional, Universidad de Oviedo, Instituto Universitario de Oncologia IUOPA, Oviedo, Spain
    PLoS ONE 5:e13242. 2010
    ..Matrix metalloproteinases (MMPs) may have pro and antifibrotic roles within the lungs, due to its ability to modulate collagen turnover and immune mediators. MMP-8 is a collagenase that also cleaves a number of cytokines and chemokines...
  64. doi request reprint Autophagy, proteases and the sense of balance
    Sandra Cabrera
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    Autophagy 6:961-3. 2010
    ..With the generation of autophagin-1/Atg4B-deficient mice, recently reported, we have progressed in our attempt to identify the in vivo physiological and pathological roles of autophagins...
  65. ncbi request reprint Identification of novel tumor suppressor proteases by degradome profiling of colorectal carcinomas
    Julia M Fraile
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Oncotarget 4:1931-2. 2013
    ..These results provide new insights into the diversity of proteases associated with cancer and support the utility of degradome profiling to identify novel proteases with tumor-defying functions. ..
  66. ncbi request reprint Protease degradomics: a new challenge for proteomics
    Carlos Lopez-Otin
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nat Rev Mol Cell Biol 3:509-19. 2002
  67. doi request reprint Matrix metalloproteinases: evolution, gene regulation and functional analysis in mouse models
    Miriam Fanjul-Fernández
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Biochim Biophys Acta 1803:3-19. 2010
    ....
  68. doi request reprint Immune-dependent and independent antitumor activity of GM-CSF aberrantly expressed by mouse and human colorectal tumors
    Rocio G Urdinguio
    Cancer Epigenetics Laboratory, HUCA, Institute of Oncology of Asturias IUOPA, Universidad de Oviedo, Oviedo, Spain
    Cancer Res 73:395-405. 2013
    ..These data suggest that expression of GM-CSF and its receptor subunits by colon tumors may be a useful marker for prognosis as well as for patient stratification in cancer immunotherapy...
  69. doi request reprint Genetic inactivation of ADAMTS15 metalloprotease in human colorectal cancer
    Cristina G Viloria
    Departamento de Bioquímica y Biología Molecular and Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Servicio de Anatomia Patologica, Hospital Central de Asturias, Oviedo, Spain
    Cancer Res 69:4926-34. 2009
    ....
  70. ncbi request reprint Autophagy and aging: new lessons from progeroid mice
    Guillermo Mariño
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    Autophagy 4:807-9. 2008
    ..Here, we analyze these unexpected findings and discuss their possible implications for the development of premature aging...
  71. pmc Increased inflammation delays wound healing in mice deficient in collagenase-2 (MMP-8)
    Ana Gutierrez-Fernandez
    Departamento de Bioquimica y Biologia Molecular, Universidad de Oviedo, 33006 Oviedo, Spain
    FASEB J 21:2580-91. 2007
    ..Taken together, these data indicate that MMP-8 participates in wound repair by contributing to the resolution of inflammation and open the possibility to develop new strategies for treating wound healing defects...
  72. pmc Loss of genes implicated in gastric function during platypus evolution
    Gonzalo R Ordóñez
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Fernando Bongera s n, 33006 Oviedo, Spain
    Genome Biol 9:R81. 2008
    ..The platypus genome sequence provides a unique opportunity to illuminate some aspects of the biology and evolution of these animals...
  73. ncbi request reprint Autophagy and aging: lessons from progeria models
    Guillermo Mariño
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, 33006 Spain
    Adv Exp Med Biol 694:61-8. 2010
    ..In this chapter, we will discuss the current knowledge on the relationship between the autophagy pathway and aging with a special emphasis on the unexpected and novel link between premature aging and autophagy up-regulation...
  74. doi request reprint Proteolytic systems: constructing degradomes
    Gonzalo R Ordóñez
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    Methods Mol Biol 539:33-47. 2009
    ..In this chapter, we review the genomic and computational methodologies used in this degradomic analysis and summarize the main findings derived from comparison of mammalian degradomes...
  75. doi request reprint Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging
    Ignacio Varela
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, calle Fernando, Bongera s n, 33006 Oviedo, Spain
    Nat Med 14:767-72. 2008
    ..Likewise, the longevity of these mice is substantially extended. These findings open a new therapeutic approach for human progeroid syndromes associated with nuclear-envelope abnormalities...
  76. ncbi request reprint Expanding the complexity of the human degradome: polyserases and their tandem serine protease domains
    Santiago Cal
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Asturias, Spain
    Front Biosci 12:4661-9. 2007
    ....
  77. pmc Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
    Xose S Puente
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nature 475:101-5. 2011
    ..It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer...
  78. doi request reprint Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide new insights into protease activation mechanisms
    Andrew J Ramsay
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Hum Mol Genet 18:3673-83. 2009
    ....
  79. pmc Protease addiction and synthetic lethality in cancer
    José M P Freije
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo Oviedo, Spain
    Front Oncol 1:25. 2011
    ....
  80. pmc Identification, functional expression and enzymic analysis of two distinct CaaX proteases from Caenorhabditis elegans
    Juan Cadinanos
    Departamento de Bioqumica y Biología Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, Campus del Cristo, 33006 Oviedo, Spain
    Biochem J 370:1047-54. 2003
    ..These results indicate that CeFACE-1 and CeFACE-2 are bona fide CaaX proteases and support the evolutionary conservation of this proteolytic system in eukaryotes...
  81. pmc Metalloproteinase MT5-MMP is an essential modulator of neuro-immune interactions in thermal pain stimulation
    Alicia R Folgueras
    Departamento de Bioquímica y Biología Molecular and Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Proc Natl Acad Sci U S A 106:16451-6. 2009
    ..Collectively, our findings demonstrate an essential role of MT5-MMP in the development of dermal neuro-immune synapses and suggest that this metalloproteinase may be a target for pain control...
  82. pmc Protective roles of matrix metalloproteinases: from mouse models to human cancer
    Carlos Lopez-Otin
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    Cell Cycle 8:3657-62. 2009
    ..Finally, the review explores the clinical applications derived from the identification of MMPs that favour the host instead of the tumor...
  83. doi request reprint The ADAMTS12 metalloprotease gene is epigenetically silenced in tumor cells and transcriptionally activated in the stroma during progression of colon cancer
    Angela Moncada-Pazos
    Departamento de Bioquimica y Biologia Molecular, Area de Fisiologia, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    J Cell Sci 122:2906-13. 2009
    ..This function is lost by epigenetic silencing in tumor cells, but concurrently induced in stromal cells, probably as part of a response of the normal tissue aimed at controlling the progression of cancer...