- Identification of c-MYC as a target of the APC pathway
T C He
Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA
Science 281:1509-12. 1998
..These results provide a molecular framework for understanding the previously enigmatic overexpression of c-MYC in colorectal cancers...
- Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC
P J Morin
Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA
Science 275:1787-90. 1997
..These results indicate that regulation of beta-catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or beta-catenin...
- Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma
Department of Immunology, University Hospital, Post Office Box 85500, 3508 GA Utrecht, Netherlands
Science 275:1784-7. 1997
..Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium...
- Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1
Dana Farber Cancer Institute, and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
Cell 98:115-24. 1999
..These data elucidate a pathway that directly links external physiological stimuli to the regulation of mitochondrial biogenesis and function...
- Coordinated transcription of key pathways in the mouse by the circadian clock
The Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA
Cell 109:307-20. 2002
..Importantly, rate-limiting steps in these various pathways were key sites of circadian control, highlighting the fundamental role that circadian clocks play in cellular and organismal physiology...
- Resveratrol improves health and survival of mice on a high-calorie diet
Joseph A Baur
Department of Pathology, Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
Nature 444:337-42. 2006
..These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing...
- Functional interaction of beta-catenin with the transcription factor LEF-1
Max Delbruck Centre for Molecular Medicine, Berlin, Germany
Nature 382:638-42. 1996
..Thus beta-catenin regulates gene expression by direct interaction with transcription factors such as LEF-1, providing a molecular mechanism for the transmission of signals, from cell-adhesion components or wnt protein to the nucleus...
- TGF-beta signal transduction
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
Annu Rev Biochem 67:753-91. 1998
..Mutations in these pathways are the cause of various forms of human cancer and developmental disorders...
- p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
Nature 398:714-8. 1999
..Taken together, our results indicate that p63 is critical for maintaining the progenitor-cell populations that are necessary to sustain epithelial development and morphogenesis...
- The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator
Department of Molecular Biology, Sciences II, University of Geneva, 30, Quai Ernest Ansermet, CH 1211 4, Geneva, Switzerland
Cell 110:251-60. 2002
..While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation...
- Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development
Department of Molecular Embryology, Max Planck Institute of Immunobiology, Stuebeweg 51, D 79108 Freiburg, Germany
Development 128:1253-64. 2001
..Our results demonstrate the pivotal role of beta-catenin in morphogenetic processes during brain and craniofacial development...
- beta-catenin is a target for the ubiquitin-proteasome pathway
Max Planck Institute for Immunobiology, Department of Molecular Embryology, Freiburg, Germany
EMBO J 16:3797-804. 1997
..We show that ubiquitination of beta-catenin is greatly reduced in Wnt-expressing cells, providing the first evidence that the ubiquitin-proteasome degradation pathway may act downstream of GSK3beta in the regulation of beta-catenin...
- Stat3 as an oncogene
J F Bromberg
Laboratory of Molecular Cell Biology, The Rockefeller University, New York, New York 10021 6399, USA
Cell 98:295-303. 1999
..Thus, the activated Stat3 molecule by itself can mediate cellular transformation and the experiments focus attention on the importance of constitutive Stat3 activation in human tumors...
- p63 Is essential for the proliferative potential of stem cells in stratified epithelia
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Cell 129:523-36. 2007
..Together, these data identify p63 as a key, lineage-specific determinant of the proliferative capacity in stem cells of stratified epithelia...
- p63 is a p53 homologue required for limb and epidermal morphogenesis
A A Mills
Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
Nature 398:708-13. 1999
..Thus, in contrast to p53, p63 is essential for several aspects of ectodermal differentiation during embryogenesis...
- STATs and gene regulation
J E Darnell
Laboratory of Molecular Cell Biology, Rockefeller University, New York, NY 10021, USA
Science 277:1630-5. 1997
..The discovery of a STAT in Drosophila, and most recently in Dictyostelium discoideum, implies an ancient evolutionary origin for this dual-function set of proteins...
- Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer
Scott A Tomlins
Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109 0602, USA
Science 310:644-8. 2005
..These results have implications in the development of carcinomas and the molecular diagnosis and treatment of prostate cancer...
- Mechanisms of TGF-beta signaling from cell membrane to the nucleus
Department of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA
Cell 113:685-700. 2003
..This article reviews these latest advances and presents our current understanding on the mechanisms of TGF-beta signaling from cell membrane to the nucleus...
- Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology and Committee on Developmental Biology, The University of Chicago, Chicago, IL 60637, USA
Development 126:4557-68. 1999
..Furthermore, our findings unveil the importance of activated LEF/TCF complexes at distinct times in hair development and cycling when changes in cell fate and differentiation commitments take place...
- System-level identification of transcriptional circuits underlying mammalian circadian clocks
Hiroki R Ueda
Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co, Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305 8585, Japan
Nat Genet 37:187-92. 2005
..Our analysis further suggests that regulation of E/E' boxes is a topological vulnerability in mammalian circadian clocks, a concept that has been functionally verified using in vitro phenotype assay systems...
- neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas
Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique Institut National de la Santé et de la Recherche Médicale Université Louis Pasteur, F 67404 Illkirch, France
Proc Natl Acad Sci U S A 97:1607-11. 2000
..Thus, ngn3 is required for the specification of a common precursor for the four pancreatic endocrine cell types...
- Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise
Joshua T Mendell
Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 539 Broadway Research Building, 733 N Broadway, Baltimore, Maryland 21205, USA
Nat Genet 36:1073-8. 2004
- Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis
Department of Microbiology and W M Keck Microbial Communities and Cell Signaling Program, University of Iowa, Iowa City, Iowa 52242, USA
J Bacteriol 185:2066-79. 2003
..Acyl-homoserine lactone quorum sensing appears to be a system that allows ordered expression of hundreds of genes during P. aeruginosa growth in culture...
- STATs in oncogenesis
Molecular Oncology Program, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida, FL 33612, USA
Oncogene 19:2474-88. 2000
..This review presents the evidence for critical roles of STATs in oncogenesis and discusses the potential for development of novel cancer therapies based on mechanistic understanding of STAT signaling. Oncogene (2000)...
- beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin
Max Delbrueck Center for Molecular Medicine, Robert Roessle Strasse 10, 13092, Berlin, Germany
Cell 105:533-45. 2001
..Further analysis demonstrates that beta-catenin is essential for fate decisions of skin stem cells: in the absence of beta-catenin, stem cells fail to differentiate into follicular keratinocytes, but instead adopt an epidermal fate...
- Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis
Sarah P Thayer
Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
Nature 425:851-6. 2003
..These data suggest that this pathway may have an early and critical role in the genesis of this cancer, and that maintenance of hedgehog signalling is important for aberrant proliferation and tumorigenesis...
- XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos
Department of Immunology University Hospital, Utrecht The Netherlands
Cell 86:391-9. 1996
..We propose that signaling by beta-catenin involves complex formation with XTcf-3, followed by nuclear translocation and activation of specific XTcf-3 target genes...
- Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene
Banyu Tsukuba Research Institute Merck, Tsukuba 300 2611, Japan
EMBO J 18:5931-42. 1999
..Some nascent microadenomas were also found in the colon. These results present experimental genetic evidence that activation of the Wnt signaling pathway can cause intestinal and colonic tumors...
- Linking colorectal cancer to Wnt signaling
MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
Cell 103:311-20. 2000
- Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay
Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 236 0004, Japan
Genes Dev 20:355-67. 2006
..Thus, the SMG-1-mediated phosphorylation of Upf1 occurs on the association of SURF with EJC, which provides the link between the EJC and recognition of PTCs and triggers NMD...
- A role for Wnt signalling in self-renewal of haematopoietic stem cells
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
Nature 423:409-14. 2003
..We conclude that the Wnt signalling pathway is critical for normal HSC homeostasis in vitro and in vivo, and provide insight into a potential molecular hierarchy of regulation of HSC development...
- DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1
S A Hahn
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Science 271:350-3. 1996
..1. These results identify DPC4 as a candidate tumor suppressor gene whose inactivation may play a role in pancreatic and possibly other human cancers...
- The transcriptional coactivators p300 and CBP are histone acetyltransferases
V V Ogryzko
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 2753, USA
Cell 87:953-9. 1996
..p300/CBP acetylates all four core histones in nucleosomes. These observations suggest that p300/CBP acetylates nucleosomes in concert with PCAF...
- Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1
Joseph T Rodgers
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nature 434:113-8. 2005
..Thus, we have identified a molecular mechanism whereby SIRT1 functions in glucose homeostasis as a modulator of PGC-1alpha. These findings have strong implications for the basic pathways of energy homeostasis, diabetes and lifespan...
- p63 identifies keratinocyte stem cells
Laboratory of Tissue Engineering IDI, Istituto Dermopatico dell Immacolata, 00040 Rome, Italy
Proc Natl Acad Sci U S A 98:3156-61. 2001
..The identification of p63 as a keratinocyte stem cell marker will be of practical importance for the clinical application of epithelial cultures in cell therapy as well as for studies on epithelial tumorigenesis...
- Control mechanism of the circadian clock for timing of cell division in vivo
Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Chuo Ku, Kobe 650 0017, Japan
Science 302:255-9. 2003
..In contrast, the circadian clockwork oscillated independently of the cell cycle in single cells. Thus, the intracellular circadian clockwork can control the cell-division cycle directly and unidirectionally in proliferating cells...
- CBP/p300 in cell growth, transformation, and development
R H Goodman
Vollum Institute, Oregon Health Sciences University, Portland 97201 USA
Genes Dev 14:1553-77. 2000
- Stepwise reprogramming of B cells into macrophages
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine Cancer Research Center, 1300 Morris Park Avenue, Bronx, NY 10461, USA
Cell 117:663-76. 2004
..Our observations indicate that C/EBPalpha and beta remodel the transcription network of B cells into that of macrophages through a series of parallel and sequential changes that require endogenous PU.1...
- A road map for those who don't know JAK-STAT
David S Aaronson
Department of Pharmacology and Biological Chemistry, Immunobiology Center, Mount Sinai School of Medicine, New York, NY 10029 USA
Science 296:1653-5. 2002
..In addition, the JAK-STAT signaling pathways are regulated by a vast array of intrinsic and environmental stimuli, which can add plasticity to the response of a cell or tissue...
- p63 is the molecular switch for initiation of an epithelial stratification program
Maranke I Koster
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA
Genes Dev 18:126-31. 2004
..Our data demonstrate that p63 plays a dual role: initiating epithelial stratification during development and maintaining proliferative potential of basal keratinocytes in mature epidermis...
- De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin
Howard Hughes Medical Institute, The University of Chicago, Illinois 60637, USA
Cell 95:605-14. 1998
..Our findings suggest that transient beta-catenin stabilization may be a key player in the long-sought epidermal signal leading to hair development and implicate aberrant beta-catenin activation in hair tumors...
- Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6
Laboratory of Molecular Cell Biology, Rockefeller University, New York, NY 10021
Science 264:95-8. 1994
..Differential activation of different STAT proteins in response to different ligands should help to explain specificity in nuclear signaling from the cell surface...
- Wnt signaling: a common theme in animal development
K M Cadigan
Howard Hughes Medical Institute, Department of Developmental Biology, Beckman Center, Stanford University Medical Center, Stanford, California 94305 5323, USA
Genes Dev 11:3286-305. 1997
- Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation
Harvard University, Department of Molecular and Cellular Biology, Cambridge, Massachusetts 02138 USA
Genes Dev 13:2072-86. 1999
..Together, the results suggest a model in which Ihh coordinates diverse aspects of skeletal morphogenesis through PTHrP-dependent and independent processes...
- Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice
Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Cell 119:121-35. 2004
..These data illustrate a central role for PGC-1alpha in the control of energy metabolism but also reveal novel systemic compensatory mechanisms and pathogenic effects of impaired energy homeostasis...
- Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin
Department of Biochemistry, Hiroshima University School of Medicine, 1 2 3, Kasumi, Minami Ku, Hiroshima 734 8551, Japan
EMBO J 17:1371-84. 1998
..These results suggest that rAxin negatively regulates the Wnt signaling pathway by interacting with GSK-3beta and beta-catenin and mediating the signal from GSK-3beta to beta-catenin...
- Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment
Department of Pathology, University of Erlangen Nurnberg, Krankenhausstrasse 8 10, 91054 Erlangen, Germany
Proc Natl Acad Sci U S A 98:10356-61. 2001
- A family of cytokine-inducible inhibitors of signalling
The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia
Nature 387:917-21. 1997
..Transcription of all four SOCS genes is increased rapidly in response to interleukin-6, in vitro and in vivo, suggesting they may act in a classic negative feedback loop to regulate cytokine signal transduction...
- Role of the TMPRSS2-ERG gene fusion in prostate cancer
Scott A Tomlins
Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Neoplasia 10:177-88. 2008
..Our results support previous work suggesting that TMPRSS2-ERG fusions mediate invasion, consistent with the defining histologic distinction between PIN and prostate cancer...
- p63 regulates proliferation and differentiation of developmentally mature keratinocytes
Amy B Truong
VA Palo Alto Health Care System, Palo Alto, California 94304, USA
Genes Dev 20:3185-97. 2006
..These data indicate that p63 is required for both the proliferative and differentiation potential of developmentally mature keratinocytes...
- The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling
Division of Gastroenterology, The Hospital for Sick Children, Toronto, Ontario, Canada
Cell 89:1165-73. 1997
..These studies thus define a novel function for MAD-related proteins as intracellular antagonists of the type I kinase domain of TGFbeta family receptors...
- Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients
Eric E Smith
Genome Center, Program in Molecular and Cellular Biology, University of Washington, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 103:8487-92. 2006
..aeruginosa strains present in advanced CF infections differ systematically from those of "wild-type" P. aeruginosa and that these differences may offer new opportunities for treatment of this chronic disease...
- Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta
Max Delbruck Center for Molecular Medicine, Robert Rossle Strasse 10, 13122 Berlin, Germany
Science 280:596-9. 1998
..Thus, conductin is a component of the multiprotein complex that directs beta-catenin to degradation and is located downstream of APC. In Xenopus embryos, conductin interfered with wnt-induced axis formation...
- Small molecule modulation of Smoothened activity
James K Chen
Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 99:14071-6. 2002
..The mechanistic differences between the Smo antagonists may be useful in the therapeutic manipulation of Hh signaling...
- Activating Smoothened mutations in sporadic basal-cell carcinoma
Department of Dermatology, San Francisco General Hospital, University of California, 94110, USA
Nature 391:90-2. 1998
..These findings support the role of SMO as a signalling component of the SHH-receptor complex and provide direct evidence that mutated SMO can function as an oncogene in BCCs...
- Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours
David M Berman
Department of Molecular Biology and Genetics and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nature 425:846-51. 2003
..Our results identify a group of common lethal malignancies in which Hh pathway activity, essential for tumour growth, is activated not by mutation but by ligand expression...
- Bacterial interference caused by autoinducing peptide variants
Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York, NY 10016, USA
Science 276:2027-30. 1997
..Cross-inhibition of gene expression represents a type of bacterial interference that could be correlated with the ability of one strain to exclude others from infection or colonization sites, or both...
- Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation
Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5G 1X5, Canada
Mol Cell 6:1365-75. 2000
..These studies thus define Smad7 as an adaptor in an E3 ubiquitin-ligase complex that targets the TGF beta receptor for degradation...
- Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate
Brett S Carver
Cancer Biology and Genetics Program, Sloan Kettering Institute, New York, New York, USA
Nat Genet 41:619-24. 2009
..Thus, ERG has a distinct role in prostate cancer progression and cooperates with PTEN haploinsufficiency to promote progression of HGPIN to invasive adenocarcinoma...
- WNT signals are required for the initiation of hair follicle development
Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19104, USA
Dev Cell 2:643-53. 2002
..This phenotype indicates that activation of WNT signaling in the skin precedes, and is required for, localized expression of regulatory genes and initiation of hair follicle placode formation...
- Requirement for beta-catenin in anterior-posterior axis formation in mice
Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany
J Cell Biol 148:567-78. 2000
..Our data demonstrate that beta-catenin function is essential in anterior-posterior axis formation in the mouse, and experiments with chimeric embryos show that this function is required in the embryonic ectoderm...
- A functional genomics strategy reveals Rora as a component of the mammalian circadian clock
Trey K Sato
Genomics Institute of the Novartis Research Foundation, 10675 John J Hopkins Drive, San Diego, California 92121, USA
Neuron 43:527-37. 2004
..These results suggest that opposing activities of the orphan nuclear receptors Rora and Rev-erb alpha, which represses Bmal1 expression, are important in the maintenance of circadian clock function...
- Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis
Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium
Cell 98:147-57. 1999
..Thus, VE-cadherin/ beta-catenin signaling controls endothelial survival...
- Stat5a is mandatory for adult mammary gland development and lactogenesis
Laboratory of Biochemistry and Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases NIDDK, National Institutes of Health NIH, Bethesda, Maryland 20892 1812, USA
Genes Dev 11:179-86. 1997
..These results document that Stat5a is the principal and an obligate mediator of mammopoietic and lactogenic signaling...
- Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF
M van de Wetering
Department of Immunology, University Hospital, Utrecht, The Netherlands
Cell 88:789-99. 1997
..Epistasis analysis positions dTCF downstream of armadillo. The Armadillo-dTCF complex mediates Wingless signaling as a bipartite transcription factor...
- Human Smad3 and Smad4 are sequence-specific transcription activators
Molecular Genetics Laboratory, Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA
Mol Cell 1:611-7. 1998
..These results define a novel biochemical property of Smad proteins that is likely to play a direct role in the biologic responses to TGF beta and related ligands...
- Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog
R J Wechsler-Reya
Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, California 94305, USA
Neuron 22:103-14. 1999
..Blocking Shh function in vivo dramatically reduces GCP proliferation. These findings provide insight into the mechanisms of normal growth and tumorigenesis in the cerebellum...
- PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs
T C He
Johns Hopkins Oncology Center, Johns Hopkins University, Baltimore, Maryland 21231, USA
Cell 99:335-45. 1999
..These findings suggest that NSAIDs inhibit tumorigenesis through inhibition of PPARdelta, the gene for which is normally regulated by APC...
- Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells
Institute for Stem Cell Research, University of Edinburgh, King s Buildings, West Mains Road, Edinburgh EH9 3JQ, Scotland
Cell 113:643-55. 2003
..These findings establish a central role for Nanog in the transcription factor hierarchy that defines ES cell identity...
- Association of the APC gene product with beta-catenin
Onyx Pharmaceuticals, Richmond, CA 94806
Science 262:1731-4. 1993
..An antibody specific to beta-catenin also recognized the 95-kilodalton protein in the immunoprecipitates. These results suggest that APC is involved in cell adhesion...
- LDL-receptor-related protein 6 is a receptor for Dickkopf proteins
Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Heidelberg, Germany
Nature 411:321-5. 2001
..Thus, DKKs inhibit Wnt co-receptor function, exemplifying the modulation of LRP signalling by antagonists...
- Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Science 273:613-22. 1996
- A mechanism of repression of TGFbeta/ Smad signaling by oncogenic Ras
Cell Biology Program and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021 USA
Genes Dev 13:804-16. 1999
..Our results suggest a mechanism for the counterbalanced regulation of Smad2/Smad3 by TGFbeta and Ras signals in normal cells, and for the silencing of antimitogenic TGFbeta functions by hyperactive Ras in cancer cells...
- Hedgehog signalling in prostate regeneration, neoplasia and metastasis
Sunil S Karhadkar
Department of Molecular Biology and Genetics and the Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nature 431:707-12. 2004
..Monitoring and manipulating Hh pathway activity may thus offer significant improvements in diagnosis and treatment of prostate cancers with metastatic potential...
- Global gene expression in Staphylococcus aureus biofilms
Karen E Beenken
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, 4301 W Markham, Little Rock, AR 72205, USA
J Bacteriol 186:4665-84. 2004
..A primary theme that emerged from the analysis of these genes is that persistence within a biofilm requires an adaptive response that limits the deleterious effects of the reduced pH associated with anaerobic growth conditions...
- Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling
Ludwig Institute for Cancer Research, Uppsala, Sweden
Nature 389:631-5. 1997
..TGF-beta rapidly induces expression of Smad7 mRNA, suggesting that Smad7 may participate in a negative feedback loop to control TGF-beta responses...
- Synchronization of cellular clocks in the suprachiasmatic nucleus
Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Kobe 650 0017, Japan
Science 302:1408-12. 2003
..Na+-dependent action potentials contributed to establishing cellular synchrony and maintaining spontaneous oscillation across the SCN...
- Perp is a p63-regulated gene essential for epithelial integrity
Rebecca A Ihrie
Division of Radiation and Cancer Biology, Stanford University School of Medicine, Stanford, California 94305, USA
Cell 120:843-56. 2005
..These findings demonstrate that Perp is a key effector in the p63 developmental program, playing an essential role in an adhesion subprogram central to epithelial integrity and homeostasis...
- The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors
Vanderbilt Developmental Biology Program, Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, Tennessee 37232 2175, USA
Nat Genet 32:128-34. 2002
..These experiments provide evidence that Ptf1a expression is specifically connected to the acquisition of pancreatic fate by undifferentiated foregut endoderm...
- Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1
Mary Elizabeth Patti
Research Division, Joslin Diabetes Center, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 100:8466-71. 2003
..Decreased PGC1 expression may be responsible for decreased expression of NRF-dependent genes, leading to the metabolic disturbances characteristic of insulin resistance and DM...
- The Hedgehog and Wnt signalling pathways in cancer
Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nature 411:349-54. 2001
..This article focuses on Hh and Wnt signal transduction and reviews evidence suggesting that tumorigenesis associated with pathway activation may result from mis-specification of cells towards stem-cell or stem cell-like fates...
- Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha
Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, One Jimmy Fund Way, Boston, MA 02115, USA
EMBO J 26:1913-23. 2007
..These results have implications for understanding selective nutrient adaptation and how it might impact lifespan or metabolic diseases such as obesity and diabetes...
- Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor
Cell Biology Program, Howard Hughes Medical Institute and The Sloan Kettering Division of the Cornell University Graduate School of Medical Sciences, Memorial Sloan Kettering Cancer Center, The Rockefeller University, New York, NY 10021, USA
Genes Dev 12:186-97. 1998
..Smad6 specifically competes with Smad4 for binding to receptor-activated Smad1, yielding an apparently inactive Smad1-Smad6 complex. Therefore, Smad6 selectively antagonizes BMP-activated Smad1 by acting as a Smad4 decoy...
- Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta ), a novel PGC-1-related transcription coactivator associated with host cell factor
Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 277:1645-8. 2002
..HCF is shown to bind to both PGC-1alpha and -1beta and augment their transcriptional activity...
- Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice
D E Cressman
Department of Genetics and Medicine, University of Pennsylvania School of Medicine, 705a Stellar Chance, 422 Curie Boulevard, Philadelphia, PA 19104 6145, USA
Science 274:1379-83. 1996
- Target hub proteins serve as master regulators of development in yeast
Anthony R Borneman
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06511, USA
Genes Dev 20:435-48. 2006
..Our results indicate that target hubs can serve as master regulators whose activity is sufficient for the induction of complex developmental responses and therefore represent important regulatory nodes in biological networks...
- Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae
S J Lin
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Science 289:2126-8. 2000
..These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD...
- RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins
Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Strandboulevarden 49, DK 2100, Copenhagen, Denmark
Cell 131:887-900. 2007
..These data suggest that MDC1-mediated and RNF8-executed histone ubiquitylation protects genome integrity by licensing the DSB-flanking chromatin to concentrate repair factors near the DNA lesions...
- Quorum-sensing regulators control virulence gene expression in Vibrio cholerae
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 99:3129-34. 2002
..Together these data suggest a role for quorum sensing in modulating expression of blocks of virulence genes in a reciprocal fashion in vivo...
- Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils
Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, Japan
Immunity 10:39-49. 1999
..The mice show a polarized immune response toward the Th1 type and develop chronic enterocolitis with age. Taken together, Stat3 plays a critical role in deactivation of macrophages and neutrophils mainly exerted by IL-10...
- A binding site for Gli proteins is essential for HNF-3beta floor plate enhancer activity in transgenics and can respond to Shh in vitro
Laboratory of Developmental Biology, Osaka University, Suita, Japan
Development 124:1313-22. 1997
..These results also support the idea that Gli/Ci are evolutionary conserved transcription factors in the Hedgehog signalling pathway...
- The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion
Molecular Cell Biology Unit, Department of Molecular Biology, VIB Ghent University, B 9000, Ghent, Belgium
Mol Cell 7:1267-78. 2001
..SIP1 therefore appears to be a promoter of invasion in malignant epithelial tumors...
- A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A
X J Yang
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 2753, USA
Nature 382:319-24. 1996
..Exogenous expression of P/CAF in HeLa cells inhibits cell-cycle progression and counteracts the mitogenic activity of E1A. E1A disturbs the normal cellular interaction between p300/CBP and its associated histone acetylase...
- Autoinduction and signal transduction in the regulation of staphylococcal virulence
Richard P Novick
Program in Molecular Pathogenesis, Skirball Institute, Department of Microbiology, New York University School of Medicine, 10016, USA
Mol Microbiol 48:1429-49. 2003
..This review is an attempt to integrate a large body of data into the beginnings of a model that will hopefully help to guide research towards a full-scale test...
- Smad regulation in TGF-beta signal transduction
Ludwig Institute for Cancer Research, Box 595, SE 751 24 Uppsala, Sweden
J Cell Sci 114:4359-69. 2001
..Finally, the inhibitory Smads (I-Smads) block phosphorylation of R-Smads by the receptors and promote ubiquitination and degradation of receptor complexes, thus inhibiting signalling...
- Multiple small RNAs act additively to integrate sensory information and control quorum sensing in Vibrio harveyi
Kimberly C Tu
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
Genes Dev 21:221-33. 2007
..Other regulators appear to be involved in control of V. harveyi qrr expression, allowing the integration of additional sensory information into the regulation of quorum-sensing gene expression...
- Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway
Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
J Biol Chem 280:19587-93. 2005
..These findings suggest that contractile activity-induced activation of the p38 MAPK pathway promotes Pgc-1alpha gene expression and skeletal muscle adaptation...
- Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome
Gene A Lang
Department of Molecular Genetics, Section of Cancer Genetics, The University of Texas MD Anderson Cancer Center and The University of Texas Graduate School of Biomedical Sciences, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Cell 119:861-72. 2004
..These results provide in vivo validation for the gain-of-function properties of certain p53 missense mutations and suggest a mechanistic basis for these phenotypes...
- Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities
S R McKercher
Burnham Institute, La Jolla, CA, USA
EMBO J 15:5647-58. 1996
..While the PU.1 protein appears not to be essential for myeloid and lymphoid lineage commitment, it is absolutely required for the normal differentiation of B cells and macrophages...
- Muscle-specific expression of PPARgamma coactivator-1alpha improves exercise performance and increases peak oxygen uptake
Jennifer A Calvo
Novartis Institutes for BioMedical Research, 100 Technology Square, Cambridge, MA 02139, USA
J Appl Physiol (1985) 104:1304-12. 2008
..Thus this study demonstrates that upregulation of PGC-1alpha in muscle in vivo is sufficient to greatly improve exercise performance under various exercise paradigms as well as increase peak oxygen uptake...
- Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1
Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
FASEB J 16:1879-86. 2002
..These findings suggest that increases in PGC-1, NRF-1, and NRF-2 represent key regulatory components of the stimulation of mitochondrial biogenesis by exercise and that PGC-1 mediates the coordinated increases in GLUT4 and mitochondria...