Smad4

Summary

Gene Symbol: Smad4
Description: SMAD family member 4
Alias: DPC4, JIP, MADH4, MYHRS, mothers against decapentaplegic homolog 4, MAD homolog 4, SMAD, mothers against DPP homolog 4, deleted in pancreatic carcinoma locus 4, deletion target in pancreatic carcinoma 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 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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

Research Grants

  1. Kunxin Luo; Fiscal Year: 2014
  2. TGF-beta Signaling in Pancreatic Cancer
    Nabeel Bardeesy; Fiscal Year: 2013
  3. Xiao Jing Wang; Fiscal Year: 2014
  4. VESA M KAARTINEN; Fiscal Year: 2014
  5. Smad4 in blastocyst morphogenesis
    Yijing Chen; Fiscal Year: 2010
  6. Brian C Lewis; Fiscal Year: 2015
  7. Overexpression of ubiquitin E3 ligase WWP1 as an oncogenic factor in the prostate
    Jin Tang Dong; Fiscal Year: 2010
  8. ROBERT DANIEL BEAUCHAMP; Fiscal Year: 2016
  9. James W Freeman; Fiscal Year: 2014
  10. Martin M Matzuk; Fiscal Year: 2016

Detail Information

Publications246 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 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...
  4. 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...
  5. 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...
  6. 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 ..
  7. 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...
  8. 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...
  9. 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 ..
  10. 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...
  11. 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...
  12. 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...
  13. 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...
  14. 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...
  15. 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.
  16. 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...
  17. 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, ..
  18. 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 ..
  19. 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...
  20. 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...
  21. 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...
  22. 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...
  23. 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), ..
  24. 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...
  25. 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...
  26. 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...
  27. 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 ..
  28. 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 ..
  29. 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...
  30. 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...
  31. 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...
  32. 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...
  33. 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 ..
  34. 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...
  35. 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
    ....
  36. 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 ..
  37. 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...
  38. 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...
  39. 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...
  40. 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 ..
  41. ncbi Frequent 4-bp deletion in exon 9 of the SMAD4/MADH4 gene in familial juvenile polyposis patients
    W Friedl
    Institute of Human Genetics, University of Bonn, Bonn, Germany
    Genes Chromosomes Cancer 25:403-6. 1999
    ..Recently, germline mutations in the SMAD4/DPC4 gene (official symbol MADH4) have been found in the majority of patients suffering from FJP...
  42. 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-..
  43. ncbi Role of Smad proteins and transcription factor Sp1 in p21(Waf1/Cip1) regulation by transforming growth factor-beta
    K Pardali
    Ludwig Institute for Cancer Research, Box 595, SE 751 24 Uppsala, Sweden
    J Biol Chem 275:29244-56. 2000
    ..Previously we have reported that the intracellular effectors of TGF-beta, Smad3 and Smad4, functionally cooperate with Sp1 to activate the human p21 promoter in hepatoma HepG2 cells...
  44. ncbi Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis
    M G Sayed
    University of Iowa College of Medicine, Iowa City, Iowa, USA
    Ann Surg Oncol 9:901-6. 2002
    ..Two genes are known to predispose to JP, SMAD4 and bone morphogenetic protein receptor type 1A (BMPR1A)...
  45. 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 ..
  46. 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...
  47. pmc Loss of DPC4 expression and its correlation with clinicopathological parameters in pancreatic carcinoma
    Zhan Hua
    Peking Union Medical College, China Japan Friendship Institute of Clinical Medical Sciences, Beijing 100029, China
    World J Gastroenterol 9:2764-7. 2003
    b>DPC4 is a tumor suppressor gene on chromosome 18q21.1 that has high mutant frequencies in pancreatic carcinogenesis...
  48. 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...
  49. 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) ..
  50. 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...
  51. 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...
  52. 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...
  53. 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...
  54. 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...
  55. 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...
  56. doi FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination
    Sirio Dupont
    Department of Histology, Microbiology, and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35131 Padua, Italy
    Cell 136:123-35. 2009
    ..b>Smad4 is monoubiquitinated in lysine 519 in vivo, a modification that inhibits Smad4 by impeding association with ..
  57. doi Promoter-wide analysis of Smad4 binding sites in human epithelial cells
    Daizo Koinuma
    Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Bunkyo ku, Tokyo
    Cancer Sci 100:2133-42. 2009
    b>Smad4, the common partner Smad, is a key molecule in transforming growth factor-beta (TGF-beta) family signaling...
  58. 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...
  59. doi Expression of Smad and its signalling cascade in osteosarcoma
    Kyu Yeoun Won
    Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Korea
    Pathology 42:242-7. 2010
    ..The role and clinical implications of Smad signalling in osteosarcoma remain unclear...
  60. doi Prognostic significance of transforming growth factor beta (TGF-β) signaling axis molecules and E-cadherin in colorectal cancer
    Pavlos Lampropoulos
    First Department of Surgery, Tzaneio General Hospital, Athens, Greece
    Tumour Biol 33:1005-14. 2012
    ..the present study was to evaluate TGF-β, TGF-β type I receptor (TGF-βR1), TGF-β type II receptor (TGF-βR2), Smad4, pSmad2/3, and E-cadherin expression in colorectal carcinoma and to correlate the obtained data with other ..
  61. doi Genetic alterations of K-ras, p53, c-erbB-2, and DPC4 in pancreatic ductal adenocarcinoma and their correlation with patient survival
    Sang Hyun Shin
    Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
    Pancreas 42:216-22. 2013
    ..The objective of this study was to evaluate genetic alterations of K-ras, p53, c-erbB-2, and deleted in pancreatic cancer, locus 4 (DPC4) genes in pancreatic ductal adenocarcinoma and correlate these changes with patients' overall survival.
  62. doi Nuclear expression of Smad proteins and its prognostic significance in clear cell renal cell carcinoma
    Jeong Hwan Park
    Department of Pathology, Seoul National University College of Medicine, Seoul 110 799, South Korea
    Hum Pathol 44:2047-54. 2013
    Smad2, Smad3, and Smad4 are components of the transforming growth factor β signaling pathway associated with tumorigenesis. The expression of these proteins is associated with tumor progression and prognosis of many cancers...
  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. 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...
  65. ncbi Nomenclature: vertebrate mediators of TGFbeta family signals
    R Derynck
    Cell 87:173. 1996
  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 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)...
  68. 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...
  69. 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...
  70. 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...
  71. 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 ..
  72. 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...
  73. 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...
  74. 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...
  75. 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...
  76. pmc Common deletion of SMAD4 in juvenile polyposis is a mutational hotspot
    James R Howe
    Department of Surgery, University of Iowa College of Medicine, Iowa City, IA 52242 1086, USA
    Am J Hum Genet 70:1357-62. 2002
    ..A subset of families with JP have germline mutations in the SMAD4 (MADH4) gene and are at increased risk of GI cancers...
  77. 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...
  78. ncbi Suppression of tumorigenesis and induction of p15(ink4b) by Smad4/DPC4 in human pancreatic cancer cells
    Bailu Peng
    Department of Surgical Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 8:3628-38. 2002
    The tumor suppressor gene Smad4/DPC4, a key transcription factorin transforming growth factor beta (TGF-beta) signaling cascades,is inactivated in 50% of pancreatic adenocarcinomas...
  79. 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...
  80. pmc Repression of Smad transcriptional activity by PIASy, an inhibitor of activated STAT
    Jianyin Long
    Center for Advanced Biotechnology and Medicine, Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, State University of New Jersey, 679 Hoes Lane, Piscataway, NJ 08854, USA
    Proc Natl Acad Sci U S A 100:9791-6. 2003
    ..In an effort to identify Smad-interacting proteins by a yeast three-hybrid screen with Smad3 and Smad4 as baits, we identified PIASy, a member of the PIAS family...
  81. pmc Homeoprotein DLX-1 interacts with Smad4 and blocks a signaling pathway from activin A in hematopoietic cells
    Shigeru Chiba
    Departments of Biology and Human Genetics, Yale University, New Haven, CT 06520 8103, USA
    Proc Natl Acad Sci U S A 100:15577-82. 2003
    ..these cytokines bind to their respective receptor, a regulatory Smad is phosphorylated and becomes associated with Smad4, the common Smad, and the resulting complex translocates to the nucleus to regulate transcription...
  82. pmc A transforming growth factor beta-induced Smad3/Smad4 complex directly activates protein kinase A
    Lizhi Zhang
    Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Mol Cell Biol 24:2169-80. 2004
    ..Taken together, these data indicate an important and previously unrecognized interaction between the TGFbeta and PKA signaling pathways...
  83. 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...
  84. 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 (..
  85. ncbi Prognostic significance of the expression of Smad4 and Smad7 in human gastric carcinomas
    Y H Kim
    Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
    Ann Oncol 15:574-80. 2004
    ..Smad proteins have been identified as major components in the intracellular signaling of TGF-beta family members...
  86. ncbi Daxx mediates the small ubiquitin-like modifier-dependent transcriptional repression of Smad4
    Che Chang Chang
    Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China
    J Biol Chem 280:10164-73. 2005
    ..Here, we showed that Daxx interacts with Smad4 and represses its transcriptional activity via the C-terminal domain of Daxx...
  87. 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...
  88. 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...
  89. 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...
  90. 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...
  91. 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 ..
  92. 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 ..
  93. 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...
  94. 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.
  95. pmc Mutant p53 attenuates the SMAD-dependent transforming growth factor beta1 (TGF-beta1) signaling pathway by repressing the expression of TGF-beta receptor type II
    Eyal Kalo
    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Mol Cell Biol 27:8228-42. 2007
    ..This was exhibited by a reduction in SMAD2/3 phosphorylation and an inhibition of both the formation of SMAD2/SMAD4 complexes and the translocation of SMAD4 to the cell nucleus...
  96. doi Large genomic deletions of SMAD4, BMPR1A and PTEN in juvenile polyposis
    W A van Hattem
    Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
    Gut 57:623-7. 2008
    ..This syndrome is caused by germline mutation of either SMAD4 or BMPR1A, and possibly ENG...
  97. 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...
  98. 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...
  99. doi Inhibition of STAT3 Tyr705 phosphorylation by Smad4 suppresses transforming growth factor beta-mediated invasion and metastasis in pancreatic cancer cells
    Shujie Zhao
    Division of Hematology and Medical Oncology, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78229 3900, USA
    Cancer Res 68:4221-8. 2008
    The role of Smad4 in transforming growth factor beta (TGFbeta)-mediated epithelial-mesenchymal transition (EMT), invasion, and metastasis was investigated using isogenically matched pancreatic cancer cell lines that differed only in ..
  100. 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 ..
  101. 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.

Research Grants65

  1. Kunxin Luo; Fiscal Year: 2014
    ..In primary hepatocytes, TGF2 signals through Smad2 and Smad4 proteins...
  2. TGF-beta Signaling in Pancreatic Cancer
    Nabeel Bardeesy; Fiscal Year: 2013
    ..b>Smad4, a central TGF? pathway effector, is mutated in ~50% of human PDAC, and Smad4 mutations promote PDAC in mice, ..
  3. Xiao Jing Wang; Fiscal Year: 2014
    ..Aim 1 will examine molecular mechanisms of Smad4 loss-mediated HNSCC development...
  4. VESA M KAARTINEN; Fiscal Year: 2014
    ..This epithelial-specific expression of Tgf[unreadable]3, in turn, induces both Smad4-dependent (canonical) and Smad4-independent (non-canonical) signaling events in the palatal epithelium that are ..
  5. Smad4 in blastocyst morphogenesis
    Yijing Chen; Fiscal Year: 2010
    ..Conditional oocyte-specific depletion of Smad4, a key transducer of the TGF-2-related signaling, revealed a novel role for this signaling pathway in mammalian ..
  6. Brian C Lewis; Fiscal Year: 2015
    ..Loss of the Smad4 transcriptional regulator occurs in approximately half of PDAC cases, and inactivation of the TGF?RII, BMPRII, and ..
  7. 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...
  8. ROBERT DANIEL BEAUCHAMP; Fiscal Year: 2016
    ..by applicant): Prevailing experimental evidence suggests that counter-regulatory crosstalk between TGFbeta/BMP/Smad4 and Wnt/beta-catenin signaling pathways is central to normal intestinal homeostasis and that loss of this ..
  9. James W Freeman; Fiscal Year: 2014
    ..However, more than half of PDACs possess allelic deletion or inactivating mutations of the Smad4 gene...
  10. Martin M Matzuk; Fiscal Year: 2016
    ..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...
  11. Anil K Rustgi; Fiscal Year: 2016
    ..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. GLORIA HUEI TING SU; Fiscal Year: 2015
    ..Oncogene KRAS and tumor-suppressor genes p16 and SMAD4 are frequently mutated in human PDA...
  13. Effect of high fat diet on pancreatic cancer in IKKa deficient mice
    Ning Li; Fiscal Year: 2013
    ..event found in 90% of PanIN lesions and is followed by loss of different tumor suppressors, including CDK2A/INK4A, SMAD4 and TP53. Obesity is positively associated with elevated (2...
  14. Early Detection of Pancreatic Cancer Using Ice COLD-PCR
    Grant Wu; Fiscal Year: 2012
    ..mutations occur that lead to Her-2 overexpression and p16 inactivation;(3) in Stage 3, mutations occur in the TP53, DPC4, and BRCA2 genes...
  15. Alec Kimmelman; Fiscal Year: 2015
    ..of >70 mouse and human PDAC lines to determine if various genotypes (combinations of KRAS, p53, Ink4a, Smad4, Lkb1, and PTEN mutations), global gene copy number and mRNA expression profiles can predict response to HCQ as a ..
  16. 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...
  17. Regulation of Cellular Signaling Pathways by POSH
    CHARLES KENNETH KASSENBROCK; Fiscal Year: 2012
    ..This multi-protein signaling complex has been called the POSH-JIP Apoptotic Complex (PJAC)...
  18. RIK M DERYNCK; Fiscal Year: 2014
    ..transferase targets selectively a defined type of Smads, either the inhibitory Smad6 or Smad7 (Aim 1), the common Smad4 (Aim 2), or the TGF-[unreadable] - activated R-Smad Smad3 (Aim 3)...
  19. Denis Wirtz; Fiscal Year: 2016
    ..signatures that correlate with PDAC stage, response to chemotherapy, pattern of subsequent metastatic failure and SMAD4/DPC4 mutational status...
  20. Peripheral blood biopsy for molecular diagnosis of pancreatic cancer
    Sunil R Hingorani; Fiscal Year: 2013
    ..also develop assays to analyze purified PDA CTCs for clinically relevant mutations in, for example, KRAS, TP53 and DPC4. The pancreatic blood biopsy will be further refined in well characterized genetically engineered mouse models of ..
  21. 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...
  22. Molecular Motors in Transport and Signaling by APP
    Virgil Muresan; Fiscal Year: 2009
    ..Information gained throughout the study will be used to reconstitute APP/JIP-1 and APP/Fe65 motility in vitro...
  23. TYPE 1 TGF BETA RECEPTOR ALTERATIONS
    Boris Pasche; Fiscal Year: 2001
    ..Three proteins, Smad2, Smad3 and Smad4/DPC4 have been found to be essential downstream components of the TGF-beta signaling pathway in mammalian cells...
  24. Mechanism of Myostatin Action
    Shalendar Bhasin; Fiscal Year: 2013
    ..will evaluate whether Smad2 and Smad3 act as substrates for myostatin-induced phosphorylation, form complexes with Smad4, which interacts with 2 catenin either directly or through p300...
  25. Sam Thiagalingam; Fiscal Year: 2014
    ..Loss of heterozygosity (LOH) analysis and follow up studies of sporadic colon cancer enabled us to show that SMAD4 is the primary target tumor suppressor, localized to the minimally lost region at chromosome 18q21-linked to an ..
  26. Murray Korc; Fiscal Year: 2016
    ..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...
  27. TFG-Beta Isoform Signaling in Pancreatic Development
    George Gittes; Fiscal Year: 2004
    ..For example, approximately 50 percent of pancreatic ductal cancers have mutations in smad4, a critical common mediator of TGF-beta superfamily intracellular signaling...
  28. Gerald Mingin; Fiscal Year: 2014
    ..Aim 3, To determine if the TGF(-Smad4 signaling pathway is required in the process of lower genitourinary tract development...
  29. High-throughput analysis of pancreatic cancer mutations
    Scott E Kern; Fiscal Year: 2012
    ..We identified frequent mutations in the p16, SMAD4, BRCA2, and other genes, and this line of research is now reaching a period of rapid development, for the advanced ..
  30. 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...
  31. Functional Analysis of SMAD Signaling in Oocytes
    Francisco J Diaz; Fiscal Year: 2012
    ..Activated SMADs (SMAD2/3 and 1/5/9) bind SMAD4 and translocate to the nucleus where they regulate nuclear functions...
  32. MECHANISMS ON THE REGULATION OF PTEN
    YIP CHOW; Fiscal Year: 2010
    ..TGF-beta-induced PTEN suppression in our pancreatic cell models occurred in (a) SMAD4-null cells, and (b) with oncogenic K-RAS, essentially completely inhibiting SMAD-dependent signaling...
  33. Regulation of Pancreatic Tumor Progression by Disabled-2
    Barbara A Hocevar; Fiscal Year: 2010
    ..Mutation or deletion of SMAD4, a key intracellular mediator of the Smad-dependent arm of TGF? signaling, is observed in ~50% of PDAC cases and ..
  34. Punita Dhawan; Fiscal Year: 2016
    ..Here, we will: a) examine the role of APC (WT)-Smad4 axis in the regulation of Claudin-1 expression;b) determine the details of the cross-talk between APC and Smad4 in ..
  35. Role of NG2 in diabetic nephropathy
    Vesselina G Cooke; Fiscal Year: 2010
    ..aim we will specifically delete TGF-[unreadable] receptor II and its downstream intracellular signaling modulator Smad4 in NG2 positive mesangial cells...
  36. Tanner J Freeman; Fiscal Year: 2015
    ..The objective in this particular applicaton is to elucidate the role of the transcription factor Smad4 in maintaining intestinal homeostasis and how Smad4 loss contributes to colorectal cancer progression through ..
  37. Roles of Growth Factors on Corneal Morphogenesis
    Winston W Kao; Fiscal Year: 2013
    ..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 ..
  38. SARAH NICOLE FLIER; Fiscal Year: 2015
    ..evaluate the role of Smad- mediated TGF2-signaling in TNBS Crohn's colitis by experimenting in mice that lack Smad4 in intestinal epithelial cells...
  39. Mouse Model of Pancreatic Cancer Progression-Maintenance
    Nabeel Bardeesy; Fiscal Year: 2009
    ..are thought to occur at the early stages of pancreatic adenocarcinoma pathogenesis while losses of p53 and SMAD4 are associated with the emergence of more advanced lesions...
  40. CELLULAR AND MOLECULAR MECHANISMS OF GASTROINTESTINAL CANCERS
    Lopa Mishra; Fiscal Year: 2013
    ..of this P01 application, is that disruption of the TGF-B tumor suppressor pathway (through ELF, Smad3 and Smad4) leads to a proliferative potential in cells that then acquire secondary events such as activation of pathways ..
  41. 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 carrying ..
  42. Florin Selaru; Fiscal Year: 2015
    ..The reason for this restriction is that we plan on using the SMAD4/PTEN murine model of cholangiocarcinoma for our in vivo studies. Next, we propose to 2...
  43. Tim H M Huang; Fiscal Year: 2014
    ..findings, we hypothesize that epigenetic deregulation of androgen receptor, estrogen receptor a, or TGF-B/SMAD4 signaling underlies the transition of a hormone-/chemo-sensitive to a hormone-/chemo-insensitive phenotype in ..
  44. Proteins Mediating Interaction of HIV-1 and JCV in CNS
    Edward M Johnson; Fiscal Year: 2011
    ..Tissue from the Manhattan HIV Brain Bank will be used to determine whether TGF-P1 or its nuclear effectors, Smad3, Smad4 or Fasti, are localized or activated in specific cells of PML lesions...
  45. Identification of normal and cancer stem cells and their niche in oral mucosa
    Xiao Jing Wang; Fiscal Year: 2010
    ..Our unpublished data have shown that Smad4 single gene deletion (Smad4-/-) in oral epithelia results in oral cancer formation...
  46. TGF-Beta Signaling Effectors in Prostate Growth Regulation/Tumor Progression
    Natasha Kyprianou; Fiscal Year: 2013
    ..In this proposal we hypothesize that TGF- [unreadable] 1 signaling via changes in Smad4-independent intracellular effectors and cross-talk with the androgen receptor (AR) regulates prostate growth, and ..
  47. Karen M Lyons; Fiscal Year: 2016
    ..Unexpectedly, Smad4, the co-Smad that is thought to be required for complex formation in the canonical BMP signaling pathway, has a ..
  48. Shizhen Emily Wang; Fiscal Year: 2016
    ..Breast cancer cells expressing various levels of the SMAD2/3 cofactors (i.e., SMAD4, Drosha and p68) will be examined for their dynamic regulation of SMAD2/3 function and TGF-2 effect...
  49. Differential Effects of BMPs on the Healing of Craniofacial Defects
    Russell R Reid; Fiscal Year: 2013
    ..viii. To target SMAD4 signaling via si-RNA technology and examine the effects of SMAD4 inhibition both in vitro and in vivo...
  50. The Effects of Alcohol on JNK Mediated Inflammatory Signaling in Glial Cells
    Jack L Leonard; Fiscal Year: 2013
    ..pathways that controls the innate immune response and is composed of upstream kinases, JNKs, scaffolding proteins (JIP), and its down stream target, c-Jun...
  51. TGF BETA SIGNALING AND CRANIOFACIAL MORPHOGENESIS
    Yang Chai; Fiscal Year: 2009
    ..renewal application, we will carry out experiments to test the hypotheses that TGF-[unreadable] signaling mediator Smad4, its downstream target Msx1 and the interaction between Smad4 and Msx1 are crucial for the cell fate determination ..
  52. JIP mimics for the treatment of diabetes
    Maurizio Pellecchia; Fiscal Year: 2010
    ..We propose a highly integrated, multidisciplinary approach to derive novel, safe and efficacious drug-like JIP mimics and to test the most promising compounds in mice models of diabetes...
  53. 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...
  54. Yang Chai; Fiscal Year: 2016
    ..We have discovered that Smad4-mediated Bmp/Tgf-[unreadable] signaling plays a crucial role in regulating root development...
  55. Jean M Hebert; Fiscal Year: 2016
    ..In Aim 3, we determine whether and how Foxg1 participates in regulating Cdkn1a transcription in early telencephalic cells in vivo and whether Foxg1, Smad4, and Cdkn1a genetically interact.
  56. Roberto Civitelli; Fiscal Year: 2014
    ..pathways, and that the intersection of BMP and [unreadable]-catenin signaling is, at least in part, mediated by Smad4/[unreadable]-catenin interactions...
  57. Yang Chai; Fiscal Year: 2016
    ..renewal application, we will carry out experiments to test the hypotheses that TGF-[unreadable] signaling mediator Smad4, its downstream target Msx1 and the interaction between Smad4 and Msx1 are crucial for the cell fate determination ..
  58. Barbara H Jung; Fiscal Year: 2014
    ..Then, using colon cancer cell models with varying ACVR2/PI3K/SMAD4 backgrounds and activin/PI3kinase signaling manipulations, we will examine the specific mechanism of activation of ..
  59. LMP-1 is a critical regulator of BMP signaling and BMP responsiveness
    Scott D Boden; Fiscal Year: 2010
    ..of the BMP receptor (BMPR1A);and, 3) interrupting Jab1-mediated proteasomal degradation of the common Smad (Smad4)...
  60. Role of TGF-beta alterations in pancreatic cancer
    James Freeman; Fiscal Year: 2009
    ..However, more than half of PDACs possess allelic deletion or inactivating mutations of the Smad4 gene...
  61. Uses of GEM models for Translational Cancer Research
    Lynda Chin; Fiscal Year: 2013
    ..In Program 1, inducible NRAS* metastatic melanoma model and a high metastatic PTEN/SMAD4 prostate cancer model will be engineered to experience human-like cancer genome instability via incorporation of ..
  62. RESEARCH ON FUNCTIONAL GENOMICS, IMAGE ANALYSIS AND RESCUE OF CLEFT PALATE
    Yang Chai; Fiscal Year: 2013
    ..Specifically, we will use the Tgfb, Tgfbr, Smad4, Msx1 and Fgfr2 mutant animal models that represent complete and sub-mucous cleft palate defects in humans as our ..
  63. TGF-beta Signaling in Pancreatic Cancer Progression
    Christine A Iacobuzio-Donahue; Fiscal Year: 2013
    ..the patterns of pancreatic cancer failure in rapid autopsy participants and found that genetic inactivation of the DPC4 gene is highly correlated with widespread metastatic failure at autopsy...
  64. Inhibition of EP1 in conjunction with Sorafenib for liver cancer chemoprevention
    Chang Han; Fiscal Year: 2010
    ..of EP1 inhibition and sorafenib on the development of intrahepatic cholangiocellular carcinoma induced by Pten/Smad4 disruption...
  65. 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...