Metalloprotease-Disintegrin ADAM12 Expression Is Regulated by Notch Signaling via MicroRNA-29*

Metalloprotease-disintegrin ADAM12 is overexpressed and frequently mutated in breast cancer. We report here that ADAM12 expression in cultured mammalian cells is up-regulated by Notch signals. Expression of a constitutively active form of Notch1 in murine fibroblasts, myoblasts, or mammary epithelial cells or activation of the endogenous Notch signaling by co-culture with ligand-expressing cells increases ADAM12 protein and mRNA levels. Up-regulation of ADAM12 expression by Notch requires new transcription, is activated in a CSL-dependent manner, and is abolished upon inhibition of IκB kinase. Expression of a constitutively active Notch1 in NIH3T3 cells increases the stability of Adam12 mRNA. We further show that the microRNA-29 family, which has a predicted conserved site in the 3′-untranslated region of mouse Adam12, plays a critical role in mediating the stimulatory effect of Notch on ADAM12 expression. In human cells, Notch up-regulates the expression of the long form, but not the short form, of ADAM12 containing a divergent 3′-untranslated mRNA region. These studies uncover a novel paradigm in Notch signaling and establish Adam12 as a Notch-related gene.

[1]  A. Shakya,et al.  Z-DNA-forming silencer in the first exon regulates human ADAM-12 gene expression , 2010, Proceedings of the National Academy of Sciences.

[2]  S. Gygi,et al.  Proteomics identifies multipotent and low oncogenic risk stem cells of the spleen. , 2010, The international journal of biochemistry & cell biology.

[3]  A. Statnikov,et al.  The Notch/Hes1 pathway sustains NF-κB activation through CYLD repression in T cell leukemia. , 2010, Cancer cell.

[4]  D. Edwards,et al.  HDAC-mediated control of ERK- and PI3K-dependent TGF-β-induced extracellular matrix-regulating genes. , 2010, Matrix biology : journal of the International Society for Matrix Biology.

[5]  B. Ray,et al.  Transforming Growth Factor-β1–Mediated Activation of NF-κB Contributes to Enhanced ADAM-12 Expression in Mammary Carcinoma Cells , 2010, Molecular Cancer Research.

[6]  S. Bronk,et al.  Transcriptional suppression of mir‐29b‐1/mir‐29a promoter by c‐Myc, hedgehog, and NF‐kappaB , 2010, Journal of cellular biochemistry.

[7]  V. Gallo,et al.  Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal , 2010, Nature.

[8]  T. Pabst,et al.  The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML , 2010, British Journal of Cancer.

[9]  W. Filipowicz,et al.  Regulation of mRNA translation and stability by microRNAs. , 2010, Annual review of biochemistry.

[10]  E. Syta,et al.  The Role of SnoN in Transforming Growth Factor β1-induced Expression of Metalloprotease-Disintegrin ADAM12* , 2010, The Journal of Biological Chemistry.

[11]  Robert V Farese,et al.  MicroRNA-29b Regulates the Expression Level of Human Progranulin, a Secreted Glycoprotein Implicated in Frontotemporal Dementia , 2010, PloS one.

[12]  L. Liaw,et al.  Notch and Transforming Growth Factor-β (TGFβ) Signaling Pathways Cooperatively Regulate Vascular Smooth Muscle Cell Differentiation* , 2010, The Journal of Biological Chemistry.

[13]  M. Caligiuri,et al.  Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia. , 2010, Cancer cell.

[14]  V. Dixit,et al.  Signaling to NF-kappaB: regulation by ubiquitination. , 2010, Cold Spring Harbor perspectives in biology.

[15]  Yin Xiao,et al.  Stem cell-related gene expression in clonal populations of mesenchymal stromal cells from bone marrow. , 2010, Tissue engineering. Part A.

[16]  G. Sonenshein,et al.  Notch-1 activates estrogen receptor-α-dependent transcription via IKKα in breast cancer cells , 2010, Oncogene.

[17]  Ryoichiro Kageyama,et al.  Dynamic regulation of Notch signaling in neural progenitor cells. , 2009, Current opinion in cell biology.

[18]  D. Epstein,et al.  Role of miR-29b on the regulation of the extracellular matrix in human trabecular meshwork cells under chronic oxidative stress , 2009, Molecular vision.

[19]  J. Yun,et al.  Effects of MicroRNA‐29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma , 2009, Hepatology.

[20]  S. Ghosh,et al.  The NF-kappaB family of transcription factors and its regulation. , 2009, Cold Spring Harbor perspectives in biology.

[21]  P. V. van Diest,et al.  Metalloprotease ADAM10 Is Required for Notch1 Site 2 Cleavage* , 2009, The Journal of Biological Chemistry.

[22]  G. Weinmaster,et al.  Selective Use of ADAM10 and ADAM17 in Activation of Notch1 Signaling , 2009, Molecular and Cellular Biology.

[23]  C. Bloomfield,et al.  MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. , 2009, Blood.

[24]  Zhijian J. Chen,et al.  The role of ubiquitin in NF-kappaB regulatory pathways. , 2009, Annual review of biochemistry.

[25]  A. Karsan,et al.  Differential Regulation of Transforming Growth Factor β Signaling Pathways by Notch in Human Endothelial Cells* , 2009, The Journal of Biological Chemistry.

[26]  Raphael Kopan,et al.  The Canonical Notch Signaling Pathway: Unfolding the Activation Mechanism , 2009, Cell.

[27]  Danqiong Sun,et al.  The role of Delta-like 1 shedding in muscle cell self-renewal and differentiation , 2008, Journal of Cell Science.

[28]  Huating Wang,et al.  NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. , 2008, Cancer cell.

[29]  J. Visvader,et al.  Notch signaling regulates mammary stem cell function and luminal cell-fate commitment. , 2008, Cell stem cell.

[30]  U. Lendahl,et al.  Notch-1 associates with IKKα and regulates IKK activity in cervical cancer cells , 2008, Oncogene.

[31]  S. Blacklow,et al.  The molecular logic of Notch signaling – a structural and biochemical perspective , 2008, Journal of Cell Science.

[32]  Jeffrey E. Thatcher,et al.  Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis , 2008, Proceedings of the National Academy of Sciences.

[33]  Marco Marra,et al.  Transcriptome analysis of the normal human mammary cell commitment and differentiation process. , 2008, Cell stem cell.

[34]  Austin G Smith,et al.  Fibroblast growth factor induces a neural stem cell phenotype in foetal forebrain progenitors and during embryonic stem cell differentiation , 2008, Molecular and Cellular Neuroscience.

[35]  Emilia Dyczynska,et al.  Breast cancer‐associated mutations in metalloprotease disintegrin ADAM12 interfere with the intracellular trafficking and processing of the protein , 2008, International journal of cancer.

[36]  Aibin He,et al.  Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes. , 2007, Molecular endocrinology.

[37]  J. M. Thomson,et al.  Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. , 2007, Developmental biology.

[38]  C. Morrison,et al.  MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B , 2007, Proceedings of the National Academy of Sciences.

[39]  J. G. Patton,et al.  MiRNA expression analysis during normal zebrafish development and following inhibition of the Hedgehog and Notch signaling pathways , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[40]  I. Aifantis,et al.  Notches, NF-kBs and the Making of T Cell Leukemia , 2007, Cell cycle.

[41]  R. Kovall,et al.  Structures of CSL, Notch and Mastermind proteins: piecing together an active transcription complex. , 2007, Current opinion in structural biology.

[42]  E. Wentzel,et al.  A Hexanucleotide Element Directs MicroRNA Nuclear Import , 2007, Science.

[43]  C. Blobel,et al.  Proteolytic Processing of Delta-like 1 by ADAM Proteases* , 2007, Journal of Biological Chemistry.

[44]  Fang Wang,et al.  Human microRNA clusters: genomic organization and expression profile in leukemia cell lines. , 2006, Biochemical and biophysical research communications.

[45]  J. Egan,et al.  Microarray identifies ADAM family members as key responders to TGF-β1 in alveolar epithelial cells , 2006, Respiratory research.

[46]  Haiyan I. Li,et al.  Purification and unique properties of mammary epithelial stem cells , 2006, Nature.

[47]  G. Sonenshein,et al.  Notch1 augments NF‐κB activity by facilitating its nuclear retention , 2006 .

[48]  G. Baffet,et al.  Involvement of the serine/threonine p70S6 kinase in TGF-beta1-induced ADAM12 expression in cultured human hepatic stellate cells. , 2005, Journal of hepatology.

[49]  C. Croce,et al.  MicroRNA gene expression deregulation in human breast cancer. , 2005, Cancer research.

[50]  C. Bianco,et al.  Notch4 intracellular domain binding to Smad3 and inhibition of the TGF-β signaling , 2005, Oncogene.

[51]  N. Socci,et al.  Derivation of Multipotent Mesenchymal Precursors from Human Embryonic Stem Cells , 2005, PLoS medicine.

[52]  P. Kronqvist,et al.  A role for ADAM12 in breast tumor progression and stromal cell apoptosis. , 2005, Cancer research.

[53]  Eric P Hoffman,et al.  Embryonic myogenesis pathways in muscle regeneration , 2004, Developmental dynamics : an official publication of the American Association of Anatomists.

[54]  U. Lendahl,et al.  Cross-talk between the Notch and TGF-β signaling pathways mediated by interaction of the Notch intracellular domain with Smad3 , 2003, The Journal of cell biology.

[55]  Yi Cao,et al.  Role of Metalloprotease Disintegrin ADAM12 in Determination of Quiescent Reserve Cells during Myogenic Differentiation In Vitro , 2003, Molecular and Cellular Biology.

[56]  P. Sharp,et al.  Embryonic stem cell-specific MicroRNAs. , 2003, Developmental cell.

[57]  G. Dontu,et al.  In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. , 2003, Genes & development.

[58]  G. Baffet,et al.  ADAM12 in human liver cancers: TGF‐β‐regulated expression in stellate cells is associated with matrix remodeling , 2003, Hepatology.

[59]  B. de Strooper,et al.  The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts. , 2002, Human molecular genetics.

[60]  David Baltimore,et al.  CARD11 mediates factor‐specific activation of NF‐κB by the T cell receptor complex , 2002, The EMBO journal.

[61]  Yi Cao,et al.  Intracellular Processing of Metalloprotease Disintegrin ADAM12* , 2002, The Journal of Biological Chemistry.

[62]  Raphael Kopan,et al.  A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1. , 2000, Molecular cell.

[63]  A Cumano,et al.  A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. , 2000, Molecular cell.

[64]  T. Ohtsuka,et al.  Hes1 and Hes5 as Notch effectors in mammalian neuronal differentiation , 1999, The EMBO journal.

[65]  S. Blacklow,et al.  Mechanistic insights into Notch receptor signaling from structural and biochemical studies. , 2010, Current topics in developmental biology.

[66]  A. Hoffmann,et al.  The regulatory logic of the NF-kappaB signaling system. , 2010, Cold Spring Harbor Perspectives in Biology.

[67]  R. Zini,et al.  Isolation and characterization of a murine resident liver stem cell , 2008, Cell Death and Differentiation.

[68]  T. Golde,et al.  Off the beaten pathway: the complex cross talk between Notch and NF-κB , 2008, Laboratory Investigation.

[69]  T. Pierfelice,et al.  Notch, neural stem cells, and brain tumors. , 2008, Cold Spring Harbor symposia on quantitative biology.

[70]  J. Couchman,et al.  Cellular roles of ADAM12 in health and disease. , 2008, The international journal of biochemistry & cell biology.

[71]  Malay Mandal,et al.  Targeting the NF-κB signaling pathway in Notch1-induced T-cell leukemia , 2007, Nature Medicine.

[72]  C. Röcken,et al.  Increased expression of ADAM family members in human breast cancer and breast cancer cell lines , 2004, Journal of Cancer Research and Clinical Oncology.

[73]  A. Bornemann,et al.  Analysis for transcript expression of meltrin α in normal, regenerating, and denervated rat muscle , 2004, Journal of Muscle Research & Cell Motility.