Julian Downward

Summary

Affiliation: Cancer Research UK
Country: UK

Publications

  1. ncbi PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP
    Thomas Porstmann
    Gene Expression Analysis Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Oncogene 24:6465-81. 2005
  2. doi SnapShot: Ras Signaling
    Megan Cully
    Cancer Research UK London Research Institute, UK
    Cell 133:1292-1292.e1. 2008
  3. pmc RNA interference
    Julian Downward
    Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX
    BMJ 328:1245-8. 2004
  4. ncbi PI 3-kinase, Akt and cell survival
    Julian Downward
    Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Semin Cell Dev Biol 15:177-82. 2004
  5. ncbi Use of RNA interference libraries to investigate oncogenic signalling in mammalian cells
    Julian Downward
    Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Oncogene 23:8376-83. 2004
  6. pmc Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies
    Michael Steckel
    Signal Transduction, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Cell Res 22:1227-45. 2012
  7. ncbi CUTL1 is phosphorylated by protein kinase A, modulating its effects on cell proliferation and motility
    Patrick Michl
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 281:15138-44. 2006
  8. ncbi Initiation of high frequency multi-drug resistance following kinase targeting by siRNAs
    Charles Swanton
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK
    Cell Cycle 6:2001-4. 2007
  9. pmc Induction of Mxi1-SR alpha by FOXO3a contributes to repression of Myc-dependent gene expression
    Oona Delpuech
    Gene Expression Analysis Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Mol Cell Biol 27:4917-30. 2007
  10. doi Unraveling the complexity of endocrine resistance in breast cancer by functional genomics
    Charles Swanton
    Cancer Research UK London Research Institute, Signal Transduction Laboratory, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Cancer Cell 13:83-5. 2008

Detail Information

Publications70

  1. ncbi PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP
    Thomas Porstmann
    Gene Expression Analysis Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Oncogene 24:6465-81. 2005
    ..Our data indicate that activation of SREBP by Akt leads to the induction of key enzymes of the cholesterol and fatty acid biosynthesis pathways, and thus membrane lipid biosynthesis...
  2. doi SnapShot: Ras Signaling
    Megan Cully
    Cancer Research UK London Research Institute, UK
    Cell 133:1292-1292.e1. 2008
  3. pmc RNA interference
    Julian Downward
    Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX
    BMJ 328:1245-8. 2004
  4. ncbi PI 3-kinase, Akt and cell survival
    Julian Downward
    Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Semin Cell Dev Biol 15:177-82. 2004
    ..In addition, novel connections between the metabolic effects of Akt and its control of survival have recently been made...
  5. ncbi Use of RNA interference libraries to investigate oncogenic signalling in mammalian cells
    Julian Downward
    Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Oncogene 23:8376-83. 2004
    ..RNA interference library technology holds great promise for enabling somatic cell genetics in tissue culture systems. Whether it can provide significant new insights into cancer will be its greatest challenge...
  6. pmc Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies
    Michael Steckel
    Signal Transduction, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Cell Res 22:1227-45. 2012
    ..These observations suggest novel targets and new ways of combining existing therapies for optimal effect in RAS mutant cancers, which are traditionally seen as being highly refractory to therapy...
  7. ncbi CUTL1 is phosphorylated by protein kinase A, modulating its effects on cell proliferation and motility
    Patrick Michl
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 281:15138-44. 2006
    ..These data identify CUTL1 as a novel target of PKA through which this protein kinase can modulate tumor cell motility and tumor progression...
  8. ncbi Initiation of high frequency multi-drug resistance following kinase targeting by siRNAs
    Charles Swanton
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK
    Cell Cycle 6:2001-4. 2007
    ..Furthermore, this work supports efforts to identify common pathways of drug response for future drug discovery programmes...
  9. pmc Induction of Mxi1-SR alpha by FOXO3a contributes to repression of Myc-dependent gene expression
    Oona Delpuech
    Gene Expression Analysis Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Mol Cell Biol 27:4917-30. 2007
    ..Our results provide evidence of direct regulation of Mxi1 by FOXO3a and imply an additional mechanism through which the PI3-kinase/Akt/FOXO pathway can modulate Myc function...
  10. doi Unraveling the complexity of endocrine resistance in breast cancer by functional genomics
    Charles Swanton
    Cancer Research UK London Research Institute, Signal Transduction Laboratory, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Cancer Cell 13:83-5. 2008
    ..CDK10 is thus a potential biomarker for sensitivity in prospective clinical trials of patients treated with endocrine therapies...
  11. pmc Requirement for interaction of PI3-kinase p110α with RAS in lung tumor maintenance
    Esther Castellano
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Cancer Cell 24:617-30. 2013
    ..This is a tumor cell-autonomous effect, which is improved significantly by combination with MEK inhibition. Total removal of p110α expression or activity has comparable effects, albeit with greater toxicities. ..
  12. pmc HMGA2 functions as a competing endogenous RNA to promote lung cancer progression
    Madhu S Kumar
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Nature 505:212-7. 2014
    ....
  13. ncbi Involvement of MINK, a Ste20 family kinase, in Ras oncogene-induced growth arrest in human ovarian surface epithelial cells
    Barbara Nicke
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Mol Cell 20:673-85. 2005
    ..MINK is thus a distal target of Ras signaling in the induction of a growth-arrested, senescent-like phenotype that may act to oppose oncogenic transformation in HOSE cells...
  14. pmc Functional genomic analysis of drug sensitivity pathways to guide adjuvant strategies in breast cancer
    Charles Swanton
    Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, London, UK
    Breast Cancer Res 10:214. 2008
    ....
  15. doi YAP and p73: a complex affair
    Julian Downward
    Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Mol Cell 32:749-50. 2008
    ..2008) demonstrate that YAP binds p73 to activate PML transcription, which in turn mediates YAP sumoylation and stabilization, increases p73 activity, and thereby generates a DNA-damage-induced feedback loop...
  16. doi CERT depletion predicts chemotherapy benefit and mediates cytotoxic and polyploid-specific cancer cell death through autophagy induction
    Alvin J X Lee
    Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    J Pathol 226:482-94. 2012
    ....
  17. ncbi Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice
    Surbhi Gupta
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Cell 129:957-68. 2007
    ..Most importantly, they are highly resistant to endogenous Ras oncogene-induced tumorigenesis. The interaction of Ras with p110alpha is thus required in vivo for certain normal growth factor signaling and for Ras-driven tumor formation...
  18. ncbi CUTL1 is a target of TGF(beta) signaling that enhances cancer cell motility and invasiveness
    Patrick Michl
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Cancer Cell 7:521-32. 2005
    ..This suggests that CUTL1 plays a central role in coordinating a gene expression program associated with cell motility and tumor progression...
  19. doi Assessing cell size and cell cycle regulation in cells with altered TOR activity
    Megan Cully
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK
    Methods Mol Biol 821:227-37. 2012
    ..Since it regulates growth at the cellular level, cell size can be used as an indirect readout of TOR activity. Here, we describe methods used to analyze cell size in cell culture and in the Drosophila wing...
  20. pmc A role for p38 stress-activated protein kinase in regulation of cell growth via TORC1
    Megan Cully
    Signal Transduction, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom
    Mol Cell Biol 30:481-95. 2010
    ..These data suggest that p38 is an important positive regulator of TORC1 in both mammalian and Drosophila systems in response to certain stresses and growth factors...
  21. ncbi Signal transduction. Prelude to an anniversary for the RAS oncogene
    Julian Downward
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, UK
    Science 314:433-4. 2006
  22. ncbi Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs
    Charles Swanton
    Signal Transduction, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Cancer Cell 11:498-512. 2007
    ..COL4A3BP expression is increased in drug-resistant cell lines and in residual tumor following paclitaxel treatment of ovarian cancer, suggesting that it could be a target for chemotherapy-resistant cancers...
  23. pmc RAS and RHO families of GTPases directly regulate distinct phosphoinositide 3-kinase isoforms
    Ralph Fritsch
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Cell 153:1050-63. 2013
    ..These findings revise our understanding of the regulation of type I PI3K by showing that both RAS and RHO family GTPases directly regulate distinct ubiquitous PI3K isoforms and that RAC activates p110β downstream of GPCRs...
  24. ncbi The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1
    Helene Plun-Favreau
    Signal Transduction, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Cell Biol 9:1243-52. 2007
    ..We suggest that PINK1-dependent phosphorylation of HtrA2 might modulate its proteolytic activity, thereby contributing to an increased resistance of cells to mitochondrial stress...
  25. pmc Monitoring conformational changes of proteins in cells by fluorescence lifetime imaging microscopy
    Véronique Calleja
    Cell Biophysics Laboratory, London Research Institute, Cancer Research UK, Lincoln s Inn Fields Laboratory, 44 Lincoln s Inn Fields, London WC2A 3PX, U K
    Biochem J 372:33-40. 2003
    ..This novel approach of monitoring the in situ conformational changes has broad application for other members of the AGC kinase superfamily and other proteins...
  26. ncbi RNA interference libraries prove their worth in hunt for tumor suppressor genes
    Julian Downward
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Cell 121:813-5. 2005
    ..REST is a transcriptional repressor that silences neuron-specific gene expression, and PITX1 is a homeodomain transcription factor that promotes the expression of a negative regulator of Ras...
  27. ncbi Ras and phosphoinositide 3-kinase: partners in development and tumorigenesis
    Antoine R Ramjaun
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK
    Cell Cycle 6:2902-5. 2007
    ..Many questions still remain: in this Perspective, we explore the remaining uncertainties surrounding the role of this signalling mechanism, as well as the future directions that will likely shed further light on its role within cells...
  28. pmc Role of receptor tyrosine kinases in G-protein-coupled receptor regulation of Ras: transactivation or parallel pathways?
    Julian Downward
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, UK
    Biochem J 376:e9-10. 2003
    ..Epidermal growth factor receptor function is needed for basal nucleotide exchange on Ras, whereas the LPA receptor controls an inducible exchange activity...
  29. ncbi Chromosomal instability, colorectal cancer and taxane resistance
    Charles Swanton
    Royal Marsden Hospital, Department of Medicine, London, UK
    Cell Cycle 5:818-23. 2006
    ..A phase II trial of taxanes in patients with metastatic CIN negative CRC may be indicated...
  30. ncbi Targeting RAS signalling pathways in cancer therapy
    Julian Downward
    Cancer Research UK, London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Rev Cancer 3:11-22. 2003
    ..Rational therapies that target the RAS pathways might inhibit tumour growth, survival and spread. Several of these new therapeutic agents are showing promise in the clinic and many more are being developed...
  31. pmc Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids
    Mark Linch
    Department of Protein Phosphorylation, Cancer Research UK London Research Institute, London WC2A 3LY, UK
    Carcinogenesis 35:396-406. 2014
    ..The identification of a PKCι inhibitor that can restore polarized morphogenesis has implications for the treatment of Ras and ErbB2 driven malignancies. ..
  32. doi Translational responses to growth factors and stress
    Megan Cully
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Biochem Soc Trans 37:284-8. 2009
    ..In the present paper, we review mTOR-dependent and -independent translational responses, and discuss their regulation by stress...
  33. ncbi Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis
    Subham Basu
    Signal Transduction, Cancer Research UK London Research Institue, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Mol Cell 11:11-23. 2003
    ..Akt phosphorylation of YAP may thus suppress the induction of the proapoptotic gene expression response following cellular damage...
  34. doi The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer
    Madhu S Kumar
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Cell 149:642-55. 2012
    ..Discovery of the nononcogene addiction of KRAS mutant lung cancers to GATA2 presents a network of druggable pathways for therapeutic exploitation...
  35. pmc Predictive biomarker discovery through the parallel integration of clinical trial and functional genomics datasets
    Charles Swanton
    Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London, WC2A 3PX, UK
    Genome Med 2:53. 2010
    ....
  36. ncbi RNA interference, DNA methylation, and gene silencing: a bright future for cancer therapy?
    Charles Swanton
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK
    Lancet Oncol 5:653-4. 2004
  37. ncbi RNA interference-based functional genomics in cancer research--an introduction
    Julian Downward
    Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Oncogene 23:8334-5. 2004
  38. pmc The transcriptional response to Raf activation is almost completely dependent on Mitogen-activated Protein Kinase Kinase activity and shows a major autocrine component
    Almut Schulze
    Gene Expression Analysis, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom
    Mol Biol Cell 15:3450-63. 2004
    ..The use of transcriptional profiling in this way allows detailed analysis of the architecture of signaling pathways to be undertaken...
  39. ncbi Epithelial to mesenchymal transition in Madin-Darby canine kidney cells is accompanied by down-regulation of Smad3 expression, leading to resistance to transforming growth factor-beta-induced growth arrest
    Francisco J Nicolás
    Developmental Signalling Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 278:3251-6. 2003
    ..Regulation of apoptosis is not affected by Smad3 levels. These data attribute to Smad3 a critical role in the control of cell proliferation by TGF-beta, which is lost following an epithelial to mesenchymal transition...
  40. pmc RAS Interaction with PI3K: More Than Just Another Effector Pathway
    Esther Castellano
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK
    Genes Cancer 2:261-74. 2011
    ..In this review, we will summarize current knowledge about how RAS regulates one of its best-known effectors, PI3K...
  41. doi Role of RAS in the regulation of PI 3-kinase
    Esther Castellano
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, WC2A 3PX, UK
    Curr Top Microbiol Immunol 346:143-69. 2010
    ..In this chapter, we summarize current knowledge about how RAS regulates one of its best-known effectors, phosphoinositide 3-kinase (PI3K)...
  42. ncbi Binding specificity and regulation of the serine protease and PDZ domains of HtrA2/Omi
    L Miguel Martins
    Signal Transduction and Protein Isolation and Cloning Laboratories, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 278:49417-27. 2003
    ..This, together with the ability of HtrA2/Omi to degrade IAPs, may limit the overall cellular protection that can be provided by these proteins...
  43. ncbi Flicking the Warburg switch-tyrosine phosphorylation of pyruvate dehydrogenase kinase regulates mitochondrial activity in cancer cells
    Almut Schulze
    Gene Expression Analysis Laboratory, Cancer Research UK London Research Institute, London WC2A 3LY, UK
    Mol Cell 44:846-8. 2011
    ..In this issue of Molecular Cell, Hitosugi et al. (2011) show that the switch from oxidative phosphorylation to glycolysis in cancer cells is regulated by tyrosine phosphorylation of PDHK1...
  44. pmc Suppression of Egr-1 transcription through targeting of the serum response factor by oncogenic H-Ras
    Soon Young Shin
    Division of Molecular and Life Science, College of Science and Technology, Hanyang University, Ansan, Korea
    EMBO J 25:1093-103. 2006
    ..Our findings suggest a novel signaling mechanism by which prolonged activation of oncogenic H-Ras can trigger the loss of tumor suppressor Egr-1 through the PI3K pathway in NIH3T3 fibroblast model cell lines...
  45. ncbi Ras induces NBT-II epithelial cell scattering through the coordinate activities of Rac and MAPK pathways
    Natacha Edme
    Laboratoire de Régulations Cellulaires et Oncogénése UMR146, Institut Curie Section de Recherche, Centre Universitaire Paris Sud, 91405 Orsay, France
    J Cell Sci 115:2591-601. 2002
    ..Finally, coexpression of active Rac1 and active MEK1 induced the motility of NBT-II cells, suggesting that Ras mediates NBT-II cell scattering through the coordinate activation of Rac and the Raf/MAPK pathway...
  46. ncbi Fibroblast growth factor-2 induces translational regulation of Bcl-XL and Bcl-2 via a MEK-dependent pathway: correlation with resistance to etoposide-induced apoptosis
    Olivier E Pardo
    Cancer Research United Kingdom Lung Cancer Biology Group and the Medical Research Council Clinical Sciences Centre, Hammersmith Campus of Imperial College, DuCane Road, London W12 0NN, United Kingdom
    J Biol Chem 277:12040-6. 2002
    ..Thus, MEK/extracellularly regulated kinase signaling is critical in the coordinate modulation of both pro- and anti-apoptotic Bcl-2 family members by FGF-2...
  47. pmc Fibroblast growth factor 2-mediated translational control of IAPs blocks mitochondrial release of Smac/DIABLO and apoptosis in small cell lung cancer cells
    Olivier E Pardo
    Lung Cancer Biology Group, Cancer Research UK, London SW3, United Kingdom
    Mol Cell Biol 23:7600-10. 2003
    ....
  48. ncbi Role of Bim in the survival pathway induced by Raf in epithelial cells
    Michela Marani
    Cancer Research UK Molecular Oncology Unit, Imperial College London, Hammersmith Hospital, DuCane Road, London W12 0NN, UK
    Oncogene 23:2431-41. 2004
    ..This represents an important route to protect epithelial cells from the proapoptotic effect of Bim...
  49. pmc Ras and TGF[beta] cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways
    Elzbieta Janda
    Institute of Molecular Pathology, A 1030 Vienna, Austria
    J Cell Biol 156:299-313. 2002
    ..Thus, EMT seems to be a close in vitro correlate of metastasis, both requiring synergism between TGFbeta-R and Raf/MAPK signaling...
  50. pmc The extracellular matrix protein TGFBI induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel
    Ahmed Ashour Ahmed
    Functional Genomics of Drug Resistance Laboratory, Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
    Cancer Cell 12:514-27. 2007
    ..These data show that ECM can mediate taxane sensitivity by modulating microtubule stability...
  51. pmc Identification of novel gene expression targets for the Ras association domain family 1 (RASSF1A) tumor suppressor gene in non-small cell lung cancer and neuroblastoma
    Angelo Agathanggelou
    Section of Medical and Molecular Genetics, Division of Reproductive and Child Health, University of Birmingham, Birmingham B15 2TT, United Kingdom
    Cancer Res 63:5344-51. 2003
    ..The identified targets are involved in diverse cellular processes; this should help toward understanding mechanisms that contribute to RASSF1A biological activity...
  52. ncbi The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death
    Shairaz Baksh
    Cancer Biology Program, Division of Hematology and Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, 1038 NRB, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Mol Cell 18:637-50. 2005
    ..Our findings identify RASSF1A and MAP-1 as important components between death receptors and the apoptotic machinery and reveal a potential link between tumor suppression and death receptor signaling...
  53. ncbi Oncogenic Ras/Her-2 mediate hyperproliferation of polarized epithelial cells in 3D cultures and rapid tumor growth via the PI3K pathway
    Elzbieta Janda
    Institute of Molecular Pathology, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Oncogene 21:5148-59. 2002
    ..Our data thus indicate that Ras-dependent signaling through the PI3K- and MAPK pathways fulfil distinct, but complementary functions during carcinogenesis...
  54. ncbi Exoenzyme S of Pseudomonas aeruginosa is not able to induce apoptosis when cells express activated proteins, such as Ras or protein kinase B/Akt
    Anna L Jansson
    Department of Medical Biosciences Pathology, Umea University, S 901 87, Umea, Sweden
    Cell Microbiol 8:815-22. 2006
    ..In conclusion, we suggest that Ras proteins are an important cellular target for the P. aeruginosa toxin ExoS, which induces cell death during pathogenesis as a means of defending the bacterium against eukaryotic phagocytosis...
  55. pmc FGF-2 protects small cell lung cancer cells from apoptosis through a complex involving PKCepsilon, B-Raf and S6K2
    Olivier E Pardo
    Lung Cancer Biology Group, Cancer Research UK, Imperial College London, Hammersmith Hospitals Campus, Du Cane Road, London, UK
    EMBO J 25:3078-88. 2006
    ..However, increased S6K1 kinase activity has no such effect. Thus, S6K2 but not S6K1 mediates prosurvival/chemoresistance signalling...
  56. pmc Phosphoinositide 3-Kinase C2beta regulates cytoskeletal organization and cell migration via Rac-dependent mechanisms
    Roy M Katso
    Ludwig Institute for Cancer Research, Royal Free and University College Hospital Medical School, London W1W 7BS, United Kingdom
    Mol Biol Cell 17:3729-44. 2006
    ..Taken together, these findings suggest that PI3KC2beta regulates the migration and survival of human tumor cells by distinct molecular mechanisms...
  57. ncbi Cancer biology: signatures guide drug choice
    Julian Downward
    Nature 439:274-5. 2006
  58. pmc Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation
    Kazunori Inabe
    Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570 8506, Japan
    J Exp Med 195:189-200. 2002
    ..Hence, our results suggest a role for Vav3 in regulating the B cell responses by promoting the sustained production of PIP3 and thereby calcium flux...
  59. pmc Intramolecular and intermolecular interactions of protein kinase B define its activation in vivo
    Véronique Calleja
    Cell Biophysics Laboratory, Lincoln s Inn Fields Laboratories, London Research Institute, Cancer Research UK, London, United Kingdom
    PLoS Biol 5:e95. 2007
    ..This has important implications not only in extending our understanding of this oncogenic protein kinase but also in opening up distinct opportunities for therapeutic intervention...
  60. ncbi Identification of the E1A-regulated transcription factor p120 E4F as an interacting partner of the RASSF1A candidate tumor suppressor gene
    Sarah L Fenton
    Section of Medical and Molecular Genetics, Department of Reproductive and Child Health, University of Birmingham, The Medical School, Edgbaston, Birmingham, United Kingdom
    Cancer Res 64:102-7. 2004
    ..As p120(E4F) has been reported previously to interact with p14ARF, retinoblastoma, and p53, these findings provide an important link between the function of RASSF1A and other major human tumor suppressor genes...
  61. ncbi RASSF1A interacts with microtubule-associated proteins and modulates microtubule dynamics
    Ashraf Dallol
    Section of Medical and Molecular Genetics, Division of Reproductive and Child Health, University of Birmingham, The Medical School, Edgbaston, Birmingham, United Kingdom
    Cancer Res 64:4112-6. 2004
    ..Our data identify a role for RASSF1A in the regulation of microtubules and cell cycle dynamics that could be part of the mechanism(s) by which RASSF1A exerts its growth inhibition on cancer cells...
  62. ncbi Minimizing the risk of reporting false positives in large-scale RNAi screens
    Christophe J Echeverri
    Cenix BioScience GmbH, Tatzberg 47, Dresden, 10307, Germany
    Nat Methods 3:777-9. 2006
    ....
  63. ncbi CUTL1: a key mediator of TGFbeta-induced tumor invasion
    Patrick Michl
    Abteilung Innere Medizin I, Klinikum der Universität Ulm, Ulm, Germany
    Cell Cycle 5:132-4. 2006
    ..Therefore we postulate that CUTL1 might be a key mediator of the tumor-promoting effects of TGFbeta in advanced cancers...
  64. ncbi Roles of cortactin in tumor pathogenesis
    Laszlo Buday
    Department of Medical Chemistry, Semmelweis University Medical School, 9 Puskin Street, 1088 Budapest, Hungary
    Biochim Biophys Acta 1775:263-73. 2007
    ..This review aims to focus on cortactin-mediated signaling pathways, with emphasis on its contribution to tumor progression and metastasis formation...
  65. ncbi Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease
    Karsten M Strauss
    Center of Neurology and Hertie Institute for Clinical Brain Research, Leicester, UK
    Hum Mol Genet 14:2099-111. 2005
    ..On the basis of functional genomics, our results provide a novel link between mitochondrial dysfunction and neurodegeneration in PD...
  66. ncbi Mechanism of epidermal growth factor regulation of Vav2, a guanine nucleotide exchange factor for Rac
    Peter Tamas
    Department of Medical Chemistry, Semmelweis University Medical School, 9 Puskin Street, 1088 Budapest, Hungary
    J Biol Chem 278:5163-71. 2003
    ..These results suggest that EGF regulates Vav2 activity basically through phosphatidylinositol 3-kinase activation, whereas tyrosine phosphorylation of Vav2 may rather be necessary for mediating protein-protein interactions...
  67. ncbi Involvement of survival motor neuron (SMN) protein in cell death
    Sheela Vyas
    INSERM U497, 46 rue d Ulm, Paris 75005, France
    Hum Mol Genet 11:2751-64. 2002
    ..Thus, our results show that the C-terminal region is critical in suppression of apoptosis by SMN...
  68. pmc Vav1 transduces T cell receptor signals to the activation of phospholipase C-gamma1 via phosphoinositide 3-kinase-dependent and -independent pathways
    Lucinda F Reynolds
    National Institute for Medical Research, London NW7 1AA, United Kingdom
    J Exp Med 195:1103-14. 2002
    ..We show that this latter function is independent of PI3K...
  69. pmc Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis
    Michela Marani
    Molecular Oncology Unit, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom
    Mol Cell Biol 22:3577-89. 2002
    ..Furthermore, we have shown that the interaction of the BimS and BimAD isoforms with Bax leads to a conformational change in this protein analogous to that triggered by the BH3-only protein Bid...
  70. pmc PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons
    Alison Wood-Kaczmar
    Department of Molecular Neuroscience, Institute of Neurology, London, United Kingdom
    PLoS ONE 3:e2455. 2008
    ..The phenotypic effects of PINK1 loss-of-function described here in mammalian neurons provides mechanistic insight into the age-related degeneration of nigral dopaminergic neurons seen in PD...