Smad4

Summary

Gene Symbol: Smad4
Description: SMAD family member 4
Alias: DPC4, JIP, MADH4, MYHRS, MAD homolog 4, SMAD, mothers against DPP homolog 4, deleted in pancreatic carcinoma locus 4, deletion target in pancreatic carcinoma 4, mothers against decapentaplegic homolog 4, mothers against decapentaplegic, Drosophila, homolog of, 4
Species: human

Top Publications

  1. ncbi Smad4 deficiency in cervical carcinoma cells
    Stephan E Baldus
    Institute of Pathology, University of Cologne, D 50931 Cologne, Germany
    Oncogene 24:810-9. 2005
  2. ncbi Mutations in the SMAD4/DPC4 gene in juvenile polyposis
    J R Howe
    Department of Surgery, University of Iowa College of Medicine, Iowa City, IA 52242, USA
    Science 280:1086-8. 1998
  3. ncbi [Expression of Smad4 and transforming growth factor-beta1, transforming growth factor-beta receptor II in cholangiocarcinoma tissue and its biological significance]
    Bing Yuan Zhang
    Department of Hepatobiliary and Vascular Surgery, The Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, China
    Zhonghua Wai Ke Za Zhi 43:846-9. 2005
  4. ncbi Smad4 silencing in pancreatic cancer cell lines using stable RNA interference and gene expression profiles induced by transforming growth factor-beta
    Amarsanaa Jazag
    Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Oncogene 24:662-71. 2005
  5. pmc SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression
    Zhihu Ding
    Belfer Institute for Applied Cancer Science, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 470:269-73. 2011
  6. ncbi Human mRNA export machinery recruited to the 5' end of mRNA
    Hong Cheng
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 127:1389-400. 2006
  7. ncbi TGF-beta signal transduction
    J Massague
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Annu Rev Biochem 67:753-91. 1998
  8. pmc Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation
    Sophia Bornstein
    Department of Otolaryngology, Oregon Health and Science University OHSU, Portland, Oregon, USA
    J Clin Invest 119:3408-19. 2009
  9. ncbi Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription
    Y Zhang
    Department of Growth and Development, Program in Cell Biology, University of California at San Francisco, 94143 0640, USA
    Nature 394:909-13. 1998
  10. ncbi MEKK-1, a component of the stress (stress-activated protein kinase/c-Jun N-terminal kinase) pathway, can selectively activate Smad2-mediated transcriptional activation in endothelial cells
    J D Brown
    Vascular Research Division, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 274:8797-805. 1999

Detail Information

Publications218 found, 100 shown here

  1. ncbi Smad4 deficiency in cervical carcinoma cells
    Stephan E Baldus
    Institute of Pathology, University of Cologne, D 50931 Cologne, Germany
    Oncogene 24:810-9. 2005
    ..Since the TGF-beta response is mediated by Smad proteins and the tumor suppressor gene Smad4 resides at 18q21, we have analysed the Smad4 gene for cervical cancer-associated alterations in cell lines and ..
  2. ncbi Mutations in the SMAD4/DPC4 gene in juvenile polyposis
    J R Howe
    Department of Surgery, University of Iowa College of Medicine, Iowa City, IA 52242, USA
    Science 280:1086-8. 1998
    ..Here it is shown that a subset of juvenile polyposis families carry germ line mutations in the gene SMAD4 (also known as DPC4), located on chromosome 18q21...
  3. ncbi [Expression of Smad4 and transforming growth factor-beta1, transforming growth factor-beta receptor II in cholangiocarcinoma tissue and its biological significance]
    Bing Yuan Zhang
    Department of Hepatobiliary and Vascular Surgery, The Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, China
    Zhonghua Wai Ke Za Zhi 43:846-9. 2005
    To study the expression of Smad4 and transforming growth factor-beta(1) (TGFbeta(1)), transforming growth factor-beta receptor II (TGFbetaRII) in cholangiocarcinoma tissue and its relationship with the biological behaviour and prognosis ..
  4. ncbi Smad4 silencing in pancreatic cancer cell lines using stable RNA interference and gene expression profiles induced by transforming growth factor-beta
    Amarsanaa Jazag
    Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Oncogene 24:662-71. 2005
    ..The Smad4 gene is mutated or deleted in 50% of pancreatic cancers...
  5. pmc SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression
    Zhihu Ding
    Belfer Institute for Applied Cancer Science, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 470:269-73. 2011
    ..epithelium versus poorly progressive Pten-null prostate cancers revealed robust activation of the TGFβ/BMP-SMAD4 signalling axis...
  6. ncbi Human mRNA export machinery recruited to the 5' end of mRNA
    Hong Cheng
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 127:1389-400. 2006
    ..As a consequence, the mRNA would be exported in a 5' to 3' direction through the nuclear pore, as observed in early electron micrographs of giant Balbiani ring mRNPs...
  7. ncbi TGF-beta signal transduction
    J Massague
    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...
  8. pmc Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation
    Sophia Bornstein
    Department of Otolaryngology, Oregon Health and Science University OHSU, Portland, Oregon, USA
    J Clin Invest 119:3408-19. 2009
    b>Smad4 is a central mediator of TGF-beta signaling, and its expression is downregulated or lost at the malignant stage in several cancer types...
  9. ncbi Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription
    Y Zhang
    Department of Growth and Development, Program in Cell Biology, University of California at San Francisco, 94143 0640, USA
    Nature 394:909-13. 1998
    ..Smad proteins activated by receptors for TGF-beta form complexes with Smad4. These complexes are translocated into the nucleus and regulate ligand-induced gene transcription...
  10. ncbi MEKK-1, a component of the stress (stress-activated protein kinase/c-Jun N-terminal kinase) pathway, can selectively activate Smad2-mediated transcriptional activation in endothelial cells
    J D Brown
    Vascular Research Division, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 274:8797-805. 1999
    ..Activation of Smad2 by active MEKK-1 results in enhanced Smad2-Smad4 interactions, nuclear localization of Smad2 and Smad4, and the stimulation of Smad protein-transcriptional ..
  11. ncbi Germ-layer specification and control of cell growth by Ectodermin, a Smad4 ubiquitin ligase
    Sirio Dupont
    Department of Histology, Microbiology and Medical Biotechnologies, Section of Histology and Embryology, University of Padua, 35121 Padua, Italy
    Cell 121:87-99. 2005
    ..Ecto is a RING-type ubiquitin ligase for Smad4, a TGF-beta signal transducer...
  12. ncbi A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4)
    Carol J Gallione
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Lancet 363:852-9. 2004
    ..The former, an inherited gastrointestinal malignancy predisposition, is caused by mutations in MADH4 (encoding SMAD4) or BMPR1A, and the latter is a vascular malformation disorder caused by mutations in ENG (endoglin) or ACVRL1 (..
  13. doi MicroRNA-130a-mediated down-regulation of Smad4 contributes to reduced sensitivity to TGF-β1 stimulation in granulocytic precursors
    Mattias Häger
    Granulocyte Research Laboratory, Department of Haematology, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark
    Blood 118:6649-59. 2011
    b>Smad4 is important in the TGF-β pathway and required for transcriptional activation and inhibition of cell growth after TGF-β1 stimulation...
  14. doi Recruitment of TIF1γ to chromatin via its PHD finger-bromodomain activates its ubiquitin ligase and transcriptional repressor activities
    Eleonora Agricola
    Laboratory of Developmental Signalling, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Mol Cell 43:85-96. 2011
    ..TIF1γ's ability to ubiquitinate its substrate Smad4 requires its PHD finger-bromodomain, as does its transcriptional repressor activity...
  15. doi Proteomics of Smad4 regulated transforming growth factor-beta signalling in colon cancer cells
    Naveid Ahmad Ali
    Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, Australia
    Mol Biosyst 6:2332-8. 2010
    TGF-β signalling can play a paradoxical cell type specific role in cancer progression. Smad4 is a key mediator of the TGF-β pathway, and is mutated and/or deleted in many cancers...
  16. ncbi DPC4 gene in various tumor types
    M Schutte
    Gepartment of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205 2196, USA
    Cancer Res 56:2527-30. 1996
    We recently identified a novel tumor-suppressor gene, DPC4, at chromosome 18q21.1 and found that both alleles of DPC4 were inactivated in nearly one-half of the pancreatic carcinomas...
  17. ncbi A Smad transcriptional corepressor
    D Wotton
    Cell Biology Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cell 97:29-39. 1999
    Following TGFbeta receptor-mediated phosphorylation and association with Smad4, Smad2 moves into the nucleus, binds to target promoters in association with DNA-binding cofactors, and recruits coactivators such as p300/CBP to activate ..
  18. pmc Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells
    Paul D Upton
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s and Papworth Hospitals, Cambridge CB2 2QQ, UK
    J Biol Chem 284:15794-804. 2009
    ..This differential signaling may contribute to the contrasting pathologies of hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension...
  19. ncbi TGFbeta1/Smad3 counteracts BRCA1-dependent repair of DNA damage
    Anna Dubrovska
    Ludwig Institute for Cancer Research, Box 595, Biomedical Center, SE 751 24 Uppsala, Sweden
    Oncogene 24:2289-97. 2005
    ..Thus, TGFbeta1/Smad3 suppresses BRCA1-dependent DNA repair in response to a DNA damaging agent...
  20. pmc Smad4-dependent TGF-beta signaling suppresses RON receptor tyrosine kinase-dependent motility and invasion of pancreatic cancer cells
    Shujie Zhao
    Department of Medicine, Division of Medical Oncology, University of Texas Health Science Center, San Antonio, Texas 78229 3900, USA
    J Biol Chem 283:11293-301. 2008
    ..However, Smad signaling is altered by allelic deletion or intragenic mutation of the Smad4 gene in more than half of pancreatic ductal adenocarcinomas...
  21. pmc SCF(beta-TrCP1) controls Smad4 protein stability in pancreatic cancer cells
    Mei Wan
    Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    Am J Pathol 166:1379-92. 2005
    Smad4, also known as deleted in pancreatic carcinoma locus 4 (DPC4), is a critical co-factor in signal transduction pathways activated by transforming growth factor (TGF)-beta-related ligands that regulate cell growth and differentiation...
  22. ncbi Inactivation of SMAD4 tumor suppressor gene during gastric carcinoma progression
    Li Hui Wang
    Research Institute of Pharmaceutical Science, Department of Pharmacy, Seoul National University College of Pharmacy, Seoul, Korea
    Clin Cancer Res 13:102-10. 2007
    Mothers against decapentaplegic homologue 4 (SMAD4) is a tumor suppressor gene associated with gastrointestinal carcinogenesis...
  23. pmc Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins
    Z A Quinn
    Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada
    Nucleic Acids Res 29:732-42. 2001
    ..Thus, the association between Smad2 and MEF2A may subserve a physical link between TGF-ss signalling and a diverse array of genes controlled by the MEF2 cis element...
  24. doi Smad4 restoration leads to a suppression of Wnt/beta-catenin signaling activity and migration capacity in human colon carcinoma cells
    Xiaoxiao Tian
    Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou Road 1838, Guangzhou 510515, Guangdong Province, China
    Biochem Biophys Res Commun 380:478-83. 2009
    Recent studies have reported that Smad4 has a TGF-beta-independent function as a tumor suppressor in cooperating with beta-catenin/Lef to regulate target gene expression...
  25. pmc Molecular mechanism of the negative regulation of Smad1/5 protein by carboxyl terminus of Hsc70-interacting protein (CHIP)
    Le Wang
    MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China
    J Biol Chem 286:15883-94. 2011
    ..that CHIP preferentially binds to Smad1/5 and specifically disrupts the core signaling complex of Smad1/5 and Smad4. We determined the crystal structures of CHIP-TPR in complex with the phosphorylated/pseudophosphorylated Smad1 ..
  26. pmc Reduced expression of SMAD4 in gliomas correlates with progression and survival of patients
    Shi Ming He
    Department of Neurosurgery, Institute for functional neurosurgery P L A, Tangdu Hospital, Fourth Military Medical University, Xi an, 710038, PR China
    J Exp Clin Cancer Res 30:70. 2011
    To examine the expression of SMAD4 at gene and protein levels in glioma samples with different WHO grades and its association with survival.
  27. pmc BRCA1 interacts with Smad3 and regulates Smad3-mediated TGF-beta signaling during oxidative stress responses
    Huchun Li
    Division of Experimental Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 4:e7091. 2009
    ..TFG-beta activates Smad signaling via its two cell surface receptors, the TbetaRII and ALK5/TbetaRI, leading to Smad-mediated transcriptional regulation...
  28. pmc Transforming growth factor-beta1 up-regulation of human alpha(1)(I) collagen is mediated by Sp1 and Smad2 transacting factors
    Polina Sysa
    Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2195, USA
    DNA Cell Biol 28:425-34. 2009
    ..Sp1 alone or the combination of Smad2 and Smad4 activated the promoter in transfected human LX-2 stellate cells...
  29. ncbi Regulation of MCP-1 gene transcription by Smads and HIV-1 Tat in human glial cells
    Selvajothi Abraham
    Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 North 12th Street, 015 96, Room 203, Philadelphia, PA 19122, USA
    Virology 309:196-202. 2003
    ..These observations reveal a novel mechanism for Tat-mediated transcriptional activation via TGFbeta signaling pathway and provide evidence for regulation of MCP-1 gene transcription by this signaling pathway in human astrocytic cells...
  30. ncbi Distortion of autocrine transforming growth factor beta signal accelerates malignant potential by enhancing cell growth as well as PAI-1 and VEGF production in human hepatocellular carcinoma cells
    Yasushi Sugano
    Third Department of Internal Medicine, 10 15 Fumizonocho, Mariguchi, Osaka 570 8507, Japan
    Oncogene 22:2309-21. 2003
    ..Moreover, this increased TGF-beta enhanced ligand-dependent signaling through the activated Smad3 and Smad4 complex, and transcriptional activities of PAI-1 and VEGF genes...
  31. doi PARP-1 attenuates Smad-mediated transcription
    Peter Lönn
    Ludwig Institute for Cancer Research, Uppsala University, Box 595 Biomedical Center, SE 751 24 Uppsala, Sweden
    Mol Cell 40:521-32. 2010
    ..Activation of TGF-β receptors leads to phosphorylation of Smad2 and Smad3, which oligomerize with Smad4 and accumulate in the nucleus where they recognize gene regulatory regions and orchestrate transcription...
  32. pmc Aberrant p16(INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinoma
    A V Biankin
    Cancer Research Program, Garvan Institute of Medical Research, and Division of Surgery, St Vincent s Hospital, Darlinghurst, NSW 2010 Australia
    Gut 50:861-8. 2002
    ..adenocarcinoma, we examined expression of key cell cycle regulatory genes in the cyclin D1/retinoblastoma pathway and the transforming growth factor beta/Smad4 signalling pathway in a cohort of patients with surgically resected IPMT.
  33. doi MicroRNA-224 is involved in transforming growth factor-beta-mediated mouse granulosa cell proliferation and granulosa cell function by targeting Smad4
    Guidong Yao
    School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People s Republic of China
    Mol Endocrinol 24:540-51. 2010
    ..The ectopic expression of miR-224 can enhance TGF-beta1-induced GC proliferation through targeting Smad4. Inhibition of endogenous miR-224 partially suppressed GC proliferation induced by TGF-beta1...
  34. ncbi Sumoylation of Smad4, the common Smad mediator of transforming growth factor-beta family signaling
    Pierre S W Lee
    Department of Growth and Development, University of California, San Francisco, California 94143 0640, USA
    J Biol Chem 278:27853-63. 2003
    ..Receptor-activated Smads combine with a common Smad4 to translocate into the nucleus where they cooperate with other transcription factors to activate or repress ..
  35. doi Expression of Smad2 and Smad4 in cervical cancer: absent nuclear Smad4 expression correlates with poor survival
    Judith N Kloth
    Department of Pathology, The Leiden University Medical Center, Leiden, The Netherlands
    Mod Pathol 21:866-75. 2008
    Alterations in transforming growth factor-beta signaling, due to a decrease in Smad2 and especially Smad4 expression, has primarily been reported in pancreatic and colorectal cancers, although loss of the chromosomal region 18q21...
  36. ncbi Smad1 interacts with homeobox DNA-binding proteins in bone morphogenetic protein signaling
    X Shi
    Department of Pathology, University of Alabama School of Medicine, Birmingham, Alabama 35294, USA
    J Biol Chem 274:13711-7. 1999
    ..Upon phosphorylation by the BMP receptors, Smad1 interacts with Smad4 and translocates into the nucleus where the complex recruits DNA-binding protein(s) to activate specific gene ..
  37. pmc Smad4-mediated signaling inhibits intestinal neoplasia by inhibiting expression of β-catenin
    Tanner J Freeman
    Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232 2730, USA
    Gastroenterology 142:562-571.e2. 2012
    ..However, the interactions between these pathways are not clear. We investigated the effects of loss of the transcription factor Smad4 on levels of β-catenin messenger RNA (mRNA) and Wnt signaling.
  38. pmc Inhibition of pancreatic carcinoma cell growth in vitro by DPC4 gene transfection
    Wei Shen
    Department of General Surgery, Wuxi People s Hospital, Wuxi 214023, Jiangsu Province, China
    World J Gastroenterol 14:6254-60. 2008
    To detect the expression of DPC4 in malignant and non-malignant specimens of human pancreas, and observe the inhibition of retroviral pLXSN containing DPC4 on pancreatic carcinoma cells in vitro.
  39. ncbi E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression
    Chang Rung Chen
    Cell Biology Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Cell 110:19-32. 2002
    ..In response to TGFbeta, this complex moves into the nucleus and associates with Smad4, recognizing a composite Smad-E2F site on c-myc for repression...
  40. ncbi Differential ubiquitination defines the functional status of the tumor suppressor Smad4
    Anita Morén
    Ludwig Institute for Cancer Research, Box 595, Biomedical Center, SE 751 24 Uppsala, Sweden
    J Biol Chem 278:33571-82. 2003
    b>Smad4 is an essential signal transducer of all transforming growth factor-beta (TGF-beta) superfamily pathways that regulate cell growth and differentiation, and it becomes inactivated in human cancers...
  41. doi Immunohistochemical expression profile of β-catenin, E-cadherin, P-cadherin, laminin-5γ2 chain, and SMAD4 in colorectal serrated adenocarcinoma
    José García-Solano
    Department of Pathology Hospital Universitario Santa María del Rosell HUSMR, 30203 Cartagena, Spain
    Hum Pathol 43:1094-102. 2012
    ..The immunostaining patterns of β-catenin, E-cadherin, P-cadherin, laminin 5γ2, and SMAD4 and their relationship to survival were studied in different tumor areas, namely, tumor center and invasive front, ..
  42. pmc SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer
    Amanda Blackford
    Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
    Clin Cancer Res 15:4674-9. 2009
    ..Recently, the majority of protein coding genes were sequenced in a collection of pancreatic cancers, providing an unprecedented opportunity to identify genetic markers of prognosis for patients with adenocarcinoma of the pancreas...
  43. pmc SMAD proteins of oligodendroglial cells regulate transcription of JC virus early and late genes coordinately with the Tat protein of human immunodeficiency virus type 1
    Michelle R Stettner
    Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23501, USA
    J Gen Virol 90:2005-14. 2009
    ..Tat, SMAD4 and JCV large T-antigen were all visualized in oligodendroglial cells at the border of an active PML lesion in the ..
  44. pmc Antagonistic regulation of EMT by TIF1γ and Smad4 in mammary epithelial cells
    Cédric Hesling
    INSERM U1052, Centre de Recherche en Cancérologie de Lyon, F 69000 Lyon, France CNRS UMR5286, F 69000 Lyon, France Centre Leon Berard, F 69000 Lyon, France
    EMBO Rep 12:665-72. 2011
    ..A strong EMT increase was observed in TIF1γ-silenced cells after TGF-β1 treatment, whereas Smad4 inactivation completely blocked this process...
  45. pmc A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-beta signal transduction
    R H Kim
    Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA
    Genes Dev 14:1605-16. 2000
    ..However, the amino terminus of SNIP1 harbors binding sites for both Smad4 and the coactivator CBP/p300...
  46. pmc Transforming growth factor-β1 induces expression of human coagulation factor XII via Smad3 and JNK signaling pathways in human lung fibroblasts
    Ewa Jablonska
    Department of Biochemistry, Faculty of Medicine, Justus Liebig University, 35392 Giessen, Germany
    J Biol Chem 285:11638-51. 2010
    ..JNK inhibition had no effect on TGF-beta1-induced Smad3 phosphorylation, association with Smad4, and its translocation into the nucleus but strongly suppressed Smad3-DNA complex formation...
  47. ncbi Nomenclature: vertebrate mediators of TGFbeta family signals
    R Derynck
    Cell 87:173. 1996
  48. pmc Smad4 inactivation promotes malignancy and drug resistance of colon cancer
    Panagiotis Papageorgis
    Department of Medicine, Genetics and Genomics Graduate Program, Boston University School of Medicine, Boston, Massachusetts, USA
    Cancer Res 71:998-1008. 2011
    b>SMAD4 is localized to chromosome 18q21, a frequent site for loss of heterozygosity in advanced stage colon cancers...
  49. ncbi Degradation of the tumor suppressor Smad4 by WW and HECT domain ubiquitin ligases
    Anita Morén
    Ludwig Institute for Cancer Research, Box 595, Biomedical Center, Uppsala University, SE 751 24 Uppsala, Sweden
    J Biol Chem 280:22115-23. 2005
    b>Smad4 mediates signaling by the transforming growth factor-beta (TGF-beta) superfamily of cytokines. Smad signaling is negatively regulated by inhibitory (I) Smads and ubiquitin-mediated processes...
  50. ncbi Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein
    S L Stroschein
    Life Sciences Division, Lawrence Berkeley National Laboratory, and Department of Molecular and Cell Biology, University of California, Berkeley, 229 Stanley Hall, Mail Code 3206, Berkeley, CA 94720, USA
    Science 286:771-4. 1999
    ..The SnoN oncoprotein was found to interact with Smad2 and Smad4 and to repress their abilities to activate transcription through recruitment of the transcriptional corepressor N-..
  51. ncbi Smad4 and FAST-1 in the assembly of activin-responsive factor
    X Chen
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115 5730, USA
    Nature 389:85-9. 1997
    ..Activins are growth factors that act primarily through Smad2, possibly in partnership with Smad4, which forms heteromeric complexes with different ligand-specific SMADs after activation...
  52. doi Promoter methylation correlates with reduced Smad4 expression in advanced prostate cancer
    Alan A Aitchison
    Department of Oncology, Hutchison MRC Research Centre, CRUK Uro Oncology Group, University of Cambridge, Cambridge, United Kingdom
    Prostate 68:661-74. 2008
    ..A transducer of TGF-beta signaling known as Mothers against decapentaplegic homologue 4 (Smad4) is a known tumor suppressor found on chromosome 18q21...
  53. ncbi Regulation of Smad4 sumoylation and transforming growth factor-beta signaling by protein inhibitor of activated STAT1
    Min Liang
    Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 279:22857-65. 2004
    The tumor suppressor, Smad4/DPC4, is a common signal transducer in transforming growth factor-beta (TGF-beta) signaling...
  54. ncbi Novel function of androgen receptor-associated protein 55/Hic-5 as a negative regulator of Smad3 signaling
    Hui Wang
    Ireland Cancer Center Research Laboratories and Department of Pharmacology, Case Western Reserve University University Hospitals, Cleveland, OH 44106, USA
    J Biol Chem 280:5154-62. 2005
    ..In conclusion, these results support that ARA55 selectively intercepts transforming growth factor-beta signaling through an interaction of the LIM domain of ARA55 with the MH2 domain of Smad3...
  55. ncbi Analysis of SMAD4/DPC4 gene alterations in multiploid colorectal carcinomas
    Tatsuya Ando
    First Department of Internal Medicine, Iwate Medical University, Morioka, Japan
    J Gastroenterol 40:708-15. 2005
    Although recent animal studies have shown that SMAD4/DPC4 gene alterations are essential for late-stage intestinal tumorigenesis, the role of SMAD4/DPC4 gene alterations in primary human colorectal carcinomas is not fully understood...
  56. pmc SMAD4 immunohistochemistry reflects genetic status in juvenile polyposis syndrome
    Danielle Langeveld
    Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
    Clin Cancer Res 16:4126-34. 2010
    Juvenile polyposis syndrome (JPS) can be caused by a germline defect of the SMAD4 gene. Somatic inactivation of SMAD4 occurs in pancreatic and colorectal cancers and is reflected by loss of SMAD4 immunohistochemistry...
  57. doi Strong Smad4 expression correlates with poor prognosis after surgery in patients with hepatocellular carcinoma
    Kiyokazu Hiwatashi
    Department of Surgical Oncology and Digestive Surgery, Field of Oncology, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan
    Ann Surg Oncol 16:3176-82. 2009
    ..The Smad4 protein is the downstream mediator of TGF-beta...
  58. ncbi Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway
    Wei He
    Cancer Biology and Genetics Program and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Cell 125:929-41. 2006
    ..Formation of transcription regulatory complexes by the association of Smad4 with receptor-phosphorylated Smads 2 and 3 is a central event in the canonical TGFbeta pathway...
  59. pmc Mutation screening in juvenile polyposis syndrome
    Robert E Pyatt
    Department of Pathology, Ohio State University, Hamilton Hall 125, 1645 Neil Ave, Columbus, OH 43210, USA
    J Mol Diagn 8:84-8. 2006
    ..Germline mutations have been identified in MADH4 and BMPR1A, aiding in presymptomatic genetic testing...
  60. ncbi Human Smad3 and Smad4 are sequence-specific transcription activators
    L Zawel
    Molecular Genetics Laboratory, Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA
    Mol Cell 1:611-7. 1998
    ..We found that two human Smad proteins (Smad3 and Smad4) could specifically recognize an identical 8 bp palindromic sequences (GTCTAGAC)...
  61. ncbi A complex pattern of mutations and abnormal splicing of Smad4 is present in thyroid tumours
    Davide Lazzereschi
    Department of Experimental Medicine and Pathology, I Faculty of Medicine, University of Rome La Sapienza, V le Regina Elena 324, Rome 00161, Italy
    Oncogene 24:5344-54. 2005
    ..We analysed 56 thyroid tumours of various histotypes for Smad4 mutations by PCR-SSCP and sequencing, linking them to Smad4 reactivity as examined by immunohistochemistry (IHC), ..
  62. pmc High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome
    S Aretz
    Institute of Human Genetics, University of Bonn, Wilhelmstrasse 31, D 53111 Bonn, Germany
    J Med Genet 44:702-9. 2007
    In patients with juvenile polyposis syndrome (JPS) the frequency of large genomic deletions in the SMAD4 and BMPR1A genes was unknown.
  63. ncbi 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, a site that excludes DCC (a candidate suppressor gene for colorectal cancer) and includes DPC4, a gene similar in sequence to a Drosophila melanogaster gene (Mad) implicated in a transforming growth factor-beta ..
  64. doi Functional blockade of Smad4 leads to a decrease in beta-catenin levels and signaling activity in human pancreatic carcinoma cells
    Diana Romero
    Instituto de Investigaciones Biomedicas Alberto Sols, Arturo Duperier 4, 28029 Madrid, Spain
    Carcinogenesis 29:1070-6. 2008
    ..Our previous studies in murine keratinocytes led to the identification of a cooperation between oncogenic Ras and Smad4 inactivation during malignant progression...
  65. doi Deleted in pancreatic carcinoma locus 4/Smad4 participates in the regulation of apoptosis by affecting the Bcl-2/Bax balance in non-small cell lung cancer
    Zunfu Ke
    Department of Pathology, Medical School of Sun Yat sen University, Guangzhou 510080, Province Guangdong, PR China
    Hum Pathol 39:1438-45. 2008
    b>Deleted in pancreatic carcinoma locus 4 influences tumorigenesis and tumor progression by various mechanisms, including apoptosis...
  66. pmc TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4
    A Nakao
    Ludwig Institute for Cancer Research, Box 595, S 751 24 Uppsala, Sweden
    EMBO J 16:5353-62. 1997
    ..Smad2 and Smad3 are structurally highly similar and mediate TGF-beta signals. Smad4 is distantly related to Smads 2 and 3, and forms a heteromeric complex with Smad2 after TGF-beta or activin ..
  67. ncbi Basement membrane component laminin-5 is a target of the tumor suppressor Smad4
    M Zapatka
    Department of Internal Medicine, Knappschaftskrankenhaus, IMBL, Ruhr University of Bochum, Bochum, Germany
    Oncogene 26:1417-27. 2007
    The tumor suppressor Smad4 is involved in carcinogenesis mainly of the pancreas and colon...
  68. pmc Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor
    A Hata
    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
    Bone morphogenetic protein (BMP) receptors signal by phosphorylating Smad1, which then associates with Smad4; this complex moves into the nucleus and activates transcription...
  69. pmc The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations
    J R Howe
    Department of Surgery, University of Iowa College of Medicine, Iowa City, IA 52242 1086, USA
    J Med Genet 41:484-91. 2004
    ..We have identified mutations in two genes causing JP, MADH4 and bone morphogenetic protein receptor 1A (BMPR1A): both are involved in bone morphogenetic protein (BMP) ..
  70. ncbi Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling
    Y Shi
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, New Jersey 08544, USA
    Cell 94:585-94. 1998
    ..This structure establishes a framework for understanding how Smad proteins may act in concert with other transcription factors in the regulation of TGF-beta-responsive genes...
  71. ncbi Homozygous deletion of SMAD4 in breast cancer cell lines and invasive ductal carcinomas
    Diansheng Zhong
    The Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA
    Cancer Biol Ther 5:601-7. 2006
    Inactivation of TGF-beta/SMAD4 signaling was postulated to play an important role in breast cancer development...
  72. pmc Frequent loss of SMAD4/DPC4 protein in colorectal cancers
    R Salovaara
    Department of Medical Genetics, Haartman Institute, PO Box 63, FIN 00014 University of Helsinki, Finland
    Gut 51:56-9. 2002
    ..One of these, DPC4 (deleted in pancreatic cancer 4, also known as SMAD4), is mutated in a minor subset of colorectal carcinomas as well as in germlines of humans predisposed to colon ..
  73. ncbi The transforming growth factor-beta-Smad3/4 signaling pathway acts as a positive regulator for TLR2 induction by bacteria via a dual mechanism involving functional cooperation with NF-kappaB and MAPK phosphatase 1-dependent negative cross-talk with p38 MA
    Fumi Mikami
    Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 281:22397-408. 2006
    ....
  74. ncbi Functional cloning of the proto-oncogene brain factor-1 (BF-1) as a Smad-binding antagonist of transforming growth factor-beta signaling
    C Rodriguez
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    J Biol Chem 276:30224-30. 2001
    ..Our results suggest that BF-1 is a general inhibitor of TGF-beta signaling and as such may play a key role during brain development...
  75. pmc Smad4 cooperates with lymphoid enhancer-binding factor 1/T cell-specific factor to increase c-myc expression in the absence of TGF-beta signaling
    S Kyun Lim
    McArdle Laboratory for Cancer Research and Laboratory of Genetics, University of Wisconsin, Madison, WI 53706, USA
    Proc Natl Acad Sci U S A 103:18580-5. 2006
    ..b>Smad4 mediates this inhibitory effect of TGF-beta by forming a complex with Smad3, E2F4/5, and p107 at the TGF-beta ..
  76. ncbi Induction of human LTBP-3 promoter activity by TGF-beta1 is mediated by Smad3/4 and AP-1 binding elements
    Anna K Kantola
    Department of Virology, Haartman Institute and Helsinki University Hospital, University of Helsinki, Biomedicum Rm A506, P O Box 63, Haartmaninkatu 8, 00014 Helsinki, Finland
    Gene 363:142-50. 2005
    ..Our results suggest an important new role for TGF-beta1 in the regulation of its binding protein, LTBP-3...
  77. ncbi Smad4 is essential for down-regulation of E-cadherin induced by TGF-beta in pancreatic cancer cell line PANC-1
    Shinichi Takano
    Department of Immunology, University of Yamanashi, Yamanashi 409 3898, Japan
    J Biochem 141:345-51. 2007
    b>Smad4 is a tumour suppressor gene frequently deleted in pancreatic cancer...
  78. ncbi SUMO-1/Ubc9 promotes nuclear accumulation and metabolic stability of tumor suppressor Smad4
    Xia Lin
    Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 278:31043-8. 2003
    Tumor suppressor Smad4/DPC4 is a central intracellular signal transducer for transforming growth factor-beta (TGF-beta) signaling...
  79. ncbi Both Max and TFE3 cooperate with Smad proteins to bind the plasminogen activator inhibitor-1 promoter, but they have opposite effects on transcriptional activity
    Asya V Grinberg
    Howard Hughes Medical Institute and Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 278:11227-36. 2003
    ..TFE3, TFEB, and Max associated with Smad3 and Smad4 in the absence of DNA and at the PE2.1 element of the PAI-1 promoter...
  80. ncbi Human T-cell lymphotropic virus type 1 tax inhibits transforming growth factor-beta signaling by blocking the association of Smad proteins with Smad-binding element
    Dug Keun Lee
    Laboratory of Cell Regulation and Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 277:33766-75. 2002
    ..Tax directly interacts with Smad2, Smad3, and Smad4; the Smad MH2 domain binds to Tax. Furthermore, Tax inhibits Smad3.Smad4 complex formation and its DNA binding...
  81. ncbi Transforming growth factor-beta inhibits pulmonary surfactant protein B gene transcription through SMAD3 interactions with NKX2.1 and HNF-3 transcription factors
    Changgong Li
    Department of Pediatrics, Women s and Children s Hospital, University of Southern California School of Medicine, Los Angeles, California 90033, USA
    J Biol Chem 277:38399-408. 2002
    ..1 was not affected. We conclude that SMAD3 interactions with the positive regulators NKX2.1 and HNF-3 underlie the molecular basis for TGF-beta-induced repression of Sp-B gene transcription...
  82. pmc Specificity in transforming growth factor beta-induced transcription of the plasminogen activator inhibitor-1 gene: interactions of promoter DNA, transcription factor muE3, and Smad proteins
    X Hua
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 96:13130-5. 1999
    ..Because Smad3 and its partner Smad4 bind to only 4-bp Smad binding elements (SBEs) in DNA, a central question is how specificity of TGF-beta-induced ..
  83. ncbi Transforming growth factor-beta-mediated signaling via the p38 MAP kinase pathway activates Smad-dependent transcription through SUMO-1 modification of Smad4
    Takayuki Ohshima
    Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo ku, Kyoto 606 8507, Japan
    J Biol Chem 278:50833-42. 2003
    ..Here, we demonstrate that Smad4 is covalently modified by SUMO-1, which was characterized recently as a key modulator of many transcription ..
  84. ncbi Missense mutations of MADH4: characterization of the mutational hot spot and functional consequences in human tumors
    Christine A Iacobuzio-Donahue
    Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
    Clin Cancer Res 10:1597-604. 2004
    The mutational spectrum of MADH4 (DPC4/SMAD4) opens valuable insights into the functions of this protein that confer its tumor-suppressive nature in human tumors...
  85. pmc SMAD4 mutations found in unselected HHT patients
    C J Gallione
    Duke University Medical Center, Durham, NC 27710, USA
    J Med Genet 43:793-7. 2006
    ..Mutations in SMAD4, another TGF-beta pathway member, are seen in patients with the combined syndrome of juvenile polyposis (JP) and ..
  86. pmc Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway
    Yibin Kang
    Cancer Biology and Genetics Program and Howard Hughes Medical Institute, Molecular Cytology Laboratory, Memorial Sloan Kettering Cancer Center, NY 10021, USA
    Proc Natl Acad Sci U S A 102:13909-14. 2005
    ..Genetic depletion experiments further demonstrate that Smad4 contributes to the formation of osteolytic bone metastases and is essential for the induction of IL-11, a gene ..
  87. doi The rate of germline mutations and large deletions of SMAD4 and BMPR1A in juvenile polyposis
    D Calva-Cerqueira
    Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA
    Clin Genet 75:79-85. 2009
    ..Germline point mutations in SMAD4 and BMPR1A have been identified as causing JPS in approximately 40-60% of patients, but few studies have looked at ..
  88. pmc Divergent mechanisms underlie Smad4-mediated positive regulation of the three genes encoding the basement membrane component laminin-332 (laminin-5)
    Dirk Zboralski
    Department of Internal Medicine, Knappschaftskrankenhaus, IMBL, Ruhr University of Bochum, Bochum, Germany
    BMC Cancer 8:215. 2008
    Functional inactivation of the tumor suppressor Smad4 in colorectal and pancreatic carcinogenesis occurs coincident with the transition to invasive growth...
  89. ncbi Critical role of Smads and AP-1 complex in transforming growth factor-beta -dependent apoptosis
    Y Yamamura
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    J Biol Chem 275:36295-302. 2000
    ..FosB substantially enhances Smad3. Smad4-dependent transcription, and dominant-negative FosB blocks TGF-beta1-dependent apoptosis but not growth inhibition...
  90. pmc Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-beta and wnt pathways
    E Labbe
    Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, M5S 1A8
    Proc Natl Acad Sci U S A 97:8358-63. 2000
    ..Thus, our results show that TGFbeta and Wnt signaling pathways can independently or cooperatively regulate LEF1/TCF target genes and suggest a model for how these pathways can synergistically activate target genes...
  91. ncbi Homozygous deletion map at 18q21.1 in pancreatic cancer
    S A Hahn
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Cancer Res 56:490-4. 1996
    ..The homozygously deleted are contained a new candidate tumor-suppressor gene (DPC4). To date, 23 (64%) of 35 pancreatic carcinomas carry at least one homozygous deletion at a published locus...
  92. pmc Smads bind directly to the Jun family of AP-1 transcription factors
    N T Liberati
    Department of Pharmacology and Cancer Biology, Box 3813, Duke University Medical Center, Durham, NC 27708, USA
    Proc Natl Acad Sci U S A 96:4844-9. 1999
    Smad3 and Smad4 are sequence-specific DNA-binding factors that bind to their consensus DNA-binding sites in response to transforming growth factor beta (TGFbeta) and activate transcription...
  93. ncbi Sp1 and Smad proteins cooperate to mediate transforming growth factor-beta 1-induced alpha 2(I) collagen expression in human glomerular mesangial cells
    A C Poncelet
    Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois 60611 3008, USA
    J Biol Chem 276:6983-92. 2001
    ..Coimmunoprecipitation experiments demonstrate that endogenous Sp1, Smad3, and Smad4 form complexes in mesangial cells...
  94. ncbi Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor
    B Razani
    Department of Molecular Pharmacology and The Albert Einstein Cancer Center and the Departments of Medicine and Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461
    J Biol Chem 276:6727-38. 2001
    ..We localize the Type I TGF-beta receptor interaction to the scaffolding domain of Cav-1 and show that it occurs in a physiologically relevant time frame, acting to rapidly dampen signaling initiated by the TGF-beta receptor complex...
  95. ncbi Transforming growth factor-beta receptor-associated protein 1 is a Smad4 chaperone
    J U Wurthner
    Laboratory of Cell Regulation and Carcinogenesis and Laboratory of Receptor Biology and Gene Expression, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 276:19495-502. 2001
    ..that TRAP1 plays a role in the Smad-mediated signal transduction pathway, interacting with the common mediator, Smad4, in a ligand-dependent fashion...
  96. ncbi Regulation of large-scale chromatin unfolding by Smad4
    Jinghua Yan
    Beijing Institute of Biotechnology, Beijing 100850, PR China
    Biochem Biophys Res Commun 315:330-5. 2004
    The tumor suppressor Smad4 plays a critical role in the transforming growth factor-beta (TGF-beta signaling pathway. Smad4 is an essential component of transcriptional complexes mediating the activation of Smad-dependent target genes...
  97. pmc Targeted deletion of Smad4 shows it is required for transforming growth factor beta and activin signaling in colorectal cancer cells
    S Zhou
    The Howard Hughes Medical Institute at Johns Hopkins University, Baltimore, MD 21231, USA
    Proc Natl Acad Sci U S A 95:2412-6. 1998
    b>Smad4 (DPC4) is a candidate tumor suppressor gene that has been hypothesized to be critical for transmitting signals from transforming growth factor (TGF) beta and related ligands...
  98. ncbi Targeted disruption in murine cells reveals variable requirement for Smad4 in transforming growth factor beta-related signaling
    C Sirard
    Amgen Institute Ontario Cancer Institute, Toronto, Ontario M5G 2C1, Canada
    J Biol Chem 275:2063-70. 2000
    The tumor suppressor gene Smad4 has been proposed to be a common mediator of transforming growth factor beta (TGFbeta)-related signaling pathways...
  99. ncbi Role of Ras and Mapks in TGFbeta signaling
    K M Mulder
    Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Cytokine Growth Factor Rev 11:23-35. 2000
    ..elements (SBE's) in the TGFbeta(1) promoter, supershift assays suggest that at least one of these does not bind Smad4, and the other is unable to bind factors activated by TGFbeta...
  100. ncbi Non-random chromosomal rearrangements in pancreatic cancer cell lines identified by spectral karyotyping
    V Sirivatanauksorn
    Imperial Cancer Research Fund Molecular Oncology Unit, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom
    Int J Cancer 91:350-8. 2001
    ..well characterized, with mutations in the dominant oncogene KRAS and the tumour suppressor genes TP53, CDKN2A and MADH4 being typically observed...
  101. ncbi Inhibition of JNK by overexpression of the JNL binding domain of JIP-1 prevents apoptosis in sympathetic neurons
    T C Harding
    University Research Centre for Neuroendocrinology and MRC Centre for Synaptic Plasticity, University of Bristol, Marlborough Street, Bristol, BS2 8HW, UK
    J Biol Chem 276:4531-4. 2001
    ..We have therefore examined whether the JNK binding domain (JBD) of JNK-interacting protein-1 (JIP-1, a scaffold protein and specific inhibitor of JNK) can inhibit c-Jun phosphorylation and support the survival of ..

Research Grants86

  1. Regulation of TGFBeta-induced apoptosis in liver cells
    Kunxin Luo; Fiscal Year: 2007
    ..by the receptor kinases and then translocate to the nucleus, where they can form heteromeric complexes with Smad4 and activate transcription of TGFbeta responsive genes...
  2. Overexpression of ubiquitin E3 ligase WWP1 as an oncogenic factor in the prostate
    Jin Tang Dong; Fiscal Year: 2009
    ..has been shown that VWVP1 negatively regulates the TGFbeta signaling pathway by inducing the degradation of Smad2, Smad4, and TGFbeta receptor type I...
  3. Overexpression of ubiquitin E3 ligase WWP1 as an oncogenic factor in the prostate
    Jin Tang Dong; Fiscal Year: 2007
    ..has been shown that VWVP1 negatively regulates the TGFbeta signaling pathway by inducing the degradation of Smad2, Smad4, and TGFbeta receptor type I...
  4. Overexpression of ubiquitin E3 ligase WWP1 as an oncogenic factor in the prostate
    Jin Tang Dong; Fiscal Year: 2010
    ..has been shown that VWVP1 negatively regulates the TGFbeta signaling pathway by inducing the degradation of Smad2, Smad4, and TGFbeta receptor type I...
  5. SnoN and TGFbeta Signaling
    Kunxin Luo; Fiscal Year: 2005
    ..The phosphorylated R-Smads then associate with Smad4, accumulate in the nucleus and regulate transcription of TGFbeta responsive genes. The P.I...
  6. GROWTH CONTROL OF NORMAL AND MALIGNANT KERATINOCYTES
    Michael Reiss; Fiscal Year: 2007
    ..that loss of expression and/or mutational inactivation of TGFbeta receptors, or the downstream mediators Smad2 and Smad4, results in global loss of TGFbeta responsiveness in a limited subset of SCCs...
  7. TGFBeta Signaling Mechanisms in the Pancreas
    Diane Simeone; Fiscal Year: 2003
    ..DPC4 (also known as Smad4) is a signaling molecule in TGFbeta -related signaling pathways...
  8. Role of TGF beta signaling in Head Neck Squamous Cell Carcinoma progression
    Xiao Jing Wang; Fiscal Year: 2007
    ..To test our hypotheses, we will establish transgenic/knockout mouse models in which TGFbetaRII or Smad4 is deleted, or Smad7 is overexpressed in head and neck epithelia, and observe whether loss of TGFbeta signaling in ..
  9. Mechanisms of Tumorigenesis in Pancreatic Epithelial Cells
    Paul Chiao; Fiscal Year: 2009
    ..suppressed liver metastasis of pancreas cancer cells in an orthotopic nude mouse model; (4) overexpression of Smad4 inhibits tumorigenesis of pancreatic cancer cell lines...
  10. THE PanINs OF PANCREATITIS,PANCREAS CANCER AND CONTROLS
    Michael Goggins; Fiscal Year: 2002
    ..the same genetic alterations as are found in pancreatic cancer such as activation of K-ras and inactivation of p16, DPC4, p53, and BRCA2. Third, several case studies report patients with PanINs progressing to invasive pancreatic cancer...
  11. MicroRNAs and chromosome 22q in the colon
    Anil K Rustgi; Fiscal Year: 2010
    ..the chromosomal instability pathway, involving alterations in key tumor suppressor genes (APC and p53, but also SMAD4) and oncogenes (especially Ras, but also EGFR, c-myc, B-Raf) and their downstream effectors...
  12. MicroRNAs and chromosome 22q in the colon
    Anil Rustgi; Fiscal Year: 2009
    ..the chromosomal instability pathway, involving alterations in key tumor suppressor genes (APC and p53, but also SMAD4) and oncogenes (especially Ras, but also EGFR, c-myc, B-Raf) and their downstream effectors...
  13. MicroRNAs and chromosome 22q in the colon
    Anil Rustgi; Fiscal Year: 2009
    ..the chromosomal instability pathway, involving alterations in key tumor suppressor genes (APC and p53, but also SMAD4) and oncogenes (especially Ras, but also EGFR, c-myc, B-Raf) and their downstream effectors...
  14. Mutations of the type 1 TGF beta receptor in cancer
    Boris Pasche; Fiscal Year: 2002
    ..Three proteins, Smad2, Smad3 and Smad4/DPC4 have been found to be essential downstream components of the TGF-beta signaling pathway in mammalian cells...
  15. Roles of Growth Factors on Corneal Morphogenesis
    Winston W Kao; Fiscal Year: 2010
    ..e., Krt12rtTA/rtTA/tet-O-Cre/Tbr2f/f and Krt12rtTA/rtTA/tet-O-Cre/Smad4f/f in which floxed Tbr2 and Smad4 genes are ablated specifically in corneal epithelium upon doxycycline induction so that one can determine ..
  16. Roles of Growth Factors on Corneal Morphogenesis
    Winston W Kao; Fiscal Year: 2011
    ..e., Krt12rtTA/rtTA/tet-O-Cre/Tbr2f/f and Krt12rtTA/rtTA/tet-O-Cre/Smad4f/f in which floxed Tbr2 and Smad4 genes are ablated specifically in corneal epithelium upon doxycycline induction so that one can determine ..
  17. Bone Morphogenic Protein Signaling Pathways in Uterine Biology
    Martin M Matzuk; Fiscal Year: 2010
    ..receptors leads to phosphorylation of receptor-regulated SMAD proteins, which translocate to the nucleus with SMAD4 to regulate gene expression. These signaling pathways have been implicated in many pathophysiologic processes...
  18. MECHANISMS OF TGF B RECEPTOR AND SMAD SIGNALING
    Rik Derynck; Fiscal Year: 2003
    ..of Smad2 and/or 3, which then dissociate from the receptor and engage in a heteromeric complex with Smad4/DPC4. These Smads are then translocated into the nucleus where they activate transcription of defined genes...
  19. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian Lewis; Fiscal Year: 2009
    ..Activating mutations in the KRAS2 oncogene, amplification of the AKT2 oncogene, and loss of the TP53, INK4A, and MADH4 tumor suppressor genes, commonly occur in this disease...
  20. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian C Lewis; Fiscal Year: 2010
    ..Activating mutations in the KRAS2 oncogene, amplification of the AKT2 oncogene, and loss of the TP53, INK4A, and MADH4 tumor suppressor genes, commonly occur in this disease...
  21. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian Lewis; Fiscal Year: 2009
    ..Activating mutations in the KRAS2 oncogene, amplification of the AKT2 oncogene, and loss of the TP53, INK4A, and MADH4 tumor suppressor genes, commonly occur in this disease...
  22. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian C Lewis; Fiscal Year: 2010
    ..Activating mutations in the KRAS2 oncogene, amplification of the AKT2 oncogene, and loss of the TP53, INK4A, and MADH4 tumor suppressor genes, commonly occur in this disease...
  23. Dysregulation of TGF Beta Action Pancreatic Cancer
    Murray Korc; Fiscal Year: 2006
    ..PDACs) exhibit a plethora of molecular alterations that include mutations in the K-ras, p53, p16 and Smad4 genes, and overexpress multiple mitogenic growth factors and their tyrosine kinase receptors...
  24. Epithelial JNK-TGFb1 Signaling Axis in Airway Remodeling
    Yvonne Janssen Heininger; Fiscal Year: 2009
    ..Aim #4 will unravel whether JNK1 activation, c-Jun and SMAD3 linker phosphorylation, and subsequent c-Jun and SMAD4 dependent transcriptional responses within the airway epithelium are critical in the orchestration of OVA or TGF-1-..
  25. Epithelial JNK-TGFb1 Signaling Axis in Airway Remodeling
    Yvonne M W Janssen Heininger; Fiscal Year: 2010
    ..Aim #4 will unravel whether JNK1 activation, c-Jun and SMAD3 linker phosphorylation, and subsequent c-Jun and SMAD4 dependent transcriptional responses within the airway epithelium are critical in the orchestration of OVA or TGF-1-..
  26. DPC4 function in human pancreatic cancer
    Gloria Su; Fiscal Year: 2006
    ..Su's major goals. Here she proposes to study the in vivo impact of a tumor-suppressor gene, DPC4 (SMAD4/MADH4), important for human pancreatic cancer, using conditional knock-out mice and a transgenic mouse line ..
  27. FUNCTIONAL ANALYSIS OF ACTIVINS DURING DEVELOPMENT
    Martin Matzuk; Fiscal Year: 2007
    ..leads to phosphorylation of receptor-regulated SMAD proteins, which translocate to the nucleus with the common SMAD4 protein and regulate gene expression...
  28. The Effects of Alcohol on JNK Mediated Inflammatory Signaling in Glial Cells
    Jack Leonard; Fiscal Year: 2009
    ..pathways that controls the innate immune response and is composed of upstream kinases, JNKs, scaffolding proteins (JIP), and its down stream target, c-Jun...
  29. The Effects of Alcohol on JNK Mediated Inflammatory Signaling in Glial Cells
    Jack L Leonard; Fiscal Year: 2010
    ..pathways that controls the innate immune response and is composed of upstream kinases, JNKs, scaffolding proteins (JIP), and its down stream target, c-Jun...
  30. CHROMOSOME 22Q GENETIC STUDIES IN THE COLON
    Anil Rustgi; Fiscal Year: 2003
    ..polyposis coli (chromosome 5q), p53 (chromosome 17p), DCC for deleted in colon cancer (chromosome 18q), and Smad4 (chromosome 18q)...
  31. The Human Colorectal Instabilitome
    Stephen Meltzer; Fiscal Year: 2007
    ..candidate genes on protein expression and signal transduction, including phosphorylated and total SMAD2, total SMAD4, caspase 1, and TTK; 2.b...