Numb

Summary

Gene Symbol: Numb
Description: NUMB endocytic adaptor protein
Alias: protein numb homolog, numb gene homolog, numb homolog
Species: mouse
Products:     Numb

Top Publications

  1. Kuang W, Tan J, Duan Y, Duan J, Wang W, Jin F, et al. Cyclic stretch induced miR-146a upregulation delays C2C12 myogenic differentiation through inhibition of Numb. Biochem Biophys Res Commun. 2009;378:259-63 pubmed publisher
    ..Importantly, miR-146 was predicted to base-pair with sequences in the 3' UTR of Numb, which promotes satellite cell differentiation towards muscle cells by inhibiting Notch signaling...
  2. Petersen P, Zou K, Hwang J, Jan Y, Zhong W. Progenitor cell maintenance requires numb and numblike during mouse neurogenesis. Nature. 2002;419:929-34 pubmed
    ..We report here that mouse numb and numblike (Nbl), two highly conserved homologues of Drosophila numb, play redundant but critical roles in ..
  3. Dho S, Jacob S, Wolting C, French M, Rohrschneider L, McGlade C. The mammalian numb phosphotyrosine-binding domain. Characterization of binding specificity and identification of a novel PDZ domain-containing numb binding protein, LNX. J Biol Chem. 1998;273:9179-87 pubmed
    b>Numb is a phosphotyrosine-binding (PTB) domain-containing protein implicated in the control of cell fate decisions during development...
  4. Zhou Y, Atkins J, Rompani S, Bancescu D, Petersen P, Tang H, et al. The mammalian Golgi regulates numb signaling in asymmetric cell division by releasing ACBD3 during mitosis. Cell. 2007;129:163-78 pubmed
    Mammalian neural progenitor cells divide asymmetrically to self-renew and produce a neuron by segregating cytosolic Numb proteins primarily to one daughter cell...
  5. Ito T, Kwon H, Zimdahl B, Congdon K, Blum J, Lento W, et al. Regulation of myeloid leukaemia by the cell-fate determinant Musashi. Nature. 2010;466:765-8 pubmed publisher
    ..Here we have used mouse models of CML to show that disease progression is regulated by the Musashi-Numb signalling axis...
  6. Shen Q, Zhong W, Jan Y, Temple S. Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts. Development. 2002;129:4843-53 pubmed
    ..In Drosophila, unequal distribution of Numb protein during mitosis produces asymmetric cell divisions and consequently diverse neural cell fates...
  7. Anderson A, Kitchens E, Chan S, St Hill C, Jan Y, Zhong W, et al. The Notch regulator Numb links the Notch and TCR signaling pathways. J Immunol. 2005;174:890-7 pubmed
    ..The adapter protein Numb is a well-characterized inhibitor of Notch and also contains a phosphotyrosine binding domain, suggesting that Numb ..
  8. Zhong W, Jiang M, Weinmaster G, Jan L, Jan Y. Differential expression of mammalian Numb, Numblike and Notch1 suggests distinct roles during mouse cortical neurogenesis. Development. 1997;124:1887-97 pubmed
    During Drosophila neurogenesis, asymmetric cell divisions are achieved by differential segregation of Numb (d-Numb) into one of the daughter cells to cause a bias in the Notch mediated cell-cell interaction...
  9. Kuo C, Mirzadeh Z, Soriano Navarro M, Rasin M, Wang D, Shen J, et al. Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche. Cell. 2006;127:1253-64 pubmed
    ..Here we generated nestin-creER(tm) transgenic mice with inducible Cre recombinase in the SVZ and removed Numb/Numblike, key regulators of embryonic neurogenesis from postnatal SVZ progenitors and ependymal cells...
  10. Wilson A, Ardiet D, Saner C, Vilain N, Beermann F, Aguet M, et al. Normal hemopoiesis and lymphopoiesis in the combined absence of numb and numblike. J Immunol. 2007;178:6746-51 pubmed
    The mammalian ortholog of the conserved Drosophila adaptor protein Numb (Nb) and its homolog Numblike (Nbl) modulate neuronal cell fate determination at least in part by antagonizing Notch signaling...

Detail Information

Publications62

  1. Kuang W, Tan J, Duan Y, Duan J, Wang W, Jin F, et al. Cyclic stretch induced miR-146a upregulation delays C2C12 myogenic differentiation through inhibition of Numb. Biochem Biophys Res Commun. 2009;378:259-63 pubmed publisher
    ..Importantly, miR-146 was predicted to base-pair with sequences in the 3' UTR of Numb, which promotes satellite cell differentiation towards muscle cells by inhibiting Notch signaling...
  2. Petersen P, Zou K, Hwang J, Jan Y, Zhong W. Progenitor cell maintenance requires numb and numblike during mouse neurogenesis. Nature. 2002;419:929-34 pubmed
    ..We report here that mouse numb and numblike (Nbl), two highly conserved homologues of Drosophila numb, play redundant but critical roles in ..
  3. Dho S, Jacob S, Wolting C, French M, Rohrschneider L, McGlade C. The mammalian numb phosphotyrosine-binding domain. Characterization of binding specificity and identification of a novel PDZ domain-containing numb binding protein, LNX. J Biol Chem. 1998;273:9179-87 pubmed
    b>Numb is a phosphotyrosine-binding (PTB) domain-containing protein implicated in the control of cell fate decisions during development...
  4. Zhou Y, Atkins J, Rompani S, Bancescu D, Petersen P, Tang H, et al. The mammalian Golgi regulates numb signaling in asymmetric cell division by releasing ACBD3 during mitosis. Cell. 2007;129:163-78 pubmed
    Mammalian neural progenitor cells divide asymmetrically to self-renew and produce a neuron by segregating cytosolic Numb proteins primarily to one daughter cell...
  5. Ito T, Kwon H, Zimdahl B, Congdon K, Blum J, Lento W, et al. Regulation of myeloid leukaemia by the cell-fate determinant Musashi. Nature. 2010;466:765-8 pubmed publisher
    ..Here we have used mouse models of CML to show that disease progression is regulated by the Musashi-Numb signalling axis...
  6. Shen Q, Zhong W, Jan Y, Temple S. Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts. Development. 2002;129:4843-53 pubmed
    ..In Drosophila, unequal distribution of Numb protein during mitosis produces asymmetric cell divisions and consequently diverse neural cell fates...
  7. Anderson A, Kitchens E, Chan S, St Hill C, Jan Y, Zhong W, et al. The Notch regulator Numb links the Notch and TCR signaling pathways. J Immunol. 2005;174:890-7 pubmed
    ..The adapter protein Numb is a well-characterized inhibitor of Notch and also contains a phosphotyrosine binding domain, suggesting that Numb ..
  8. Zhong W, Jiang M, Weinmaster G, Jan L, Jan Y. Differential expression of mammalian Numb, Numblike and Notch1 suggests distinct roles during mouse cortical neurogenesis. Development. 1997;124:1887-97 pubmed
    During Drosophila neurogenesis, asymmetric cell divisions are achieved by differential segregation of Numb (d-Numb) into one of the daughter cells to cause a bias in the Notch mediated cell-cell interaction...
  9. Kuo C, Mirzadeh Z, Soriano Navarro M, Rasin M, Wang D, Shen J, et al. Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche. Cell. 2006;127:1253-64 pubmed
    ..Here we generated nestin-creER(tm) transgenic mice with inducible Cre recombinase in the SVZ and removed Numb/Numblike, key regulators of embryonic neurogenesis from postnatal SVZ progenitors and ependymal cells...
  10. Wilson A, Ardiet D, Saner C, Vilain N, Beermann F, Aguet M, et al. Normal hemopoiesis and lymphopoiesis in the combined absence of numb and numblike. J Immunol. 2007;178:6746-51 pubmed
    The mammalian ortholog of the conserved Drosophila adaptor protein Numb (Nb) and its homolog Numblike (Nbl) modulate neuronal cell fate determination at least in part by antagonizing Notch signaling...
  11. Petersen P, Zou K, Krauss S, Zhong W. Continuing role for mouse Numb and Numbl in maintaining progenitor cells during cortical neurogenesis. Nat Neurosci. 2004;7:803-11 pubmed
    ..Mouse Numb (also known as m-numb) and Numbl (also known as numblike or Nbl) are redundant but essential in maintaining ..
  12. Di Marcotullio L, Greco A, Mazza D, Canettieri G, Pietrosanti L, Infante P, et al. Numb activates the E3 ligase Itch to control Gli1 function through a novel degradation signal. Oncogene. 2011;30:65-76 pubmed publisher
    ..mechanism of Gli1 degradation, promoted by the coordinated action of the E3 ligase Itch and the adaptor protein Numb. We show that Numb activates the catalytic activity of Itch, releasing it from an inhibitory intramolecular ..
  13. Imai T, Tokunaga A, Yoshida T, Hashimoto M, Mikoshiba K, Weinmaster G, et al. The neural RNA-binding protein Musashi1 translationally regulates mammalian numb gene expression by interacting with its mRNA. Mol Cell Biol. 2001;21:3888-900 pubmed
    ..These consensus elements were identified in some neural mRNAs. One of these, mammalian numb (m-numb), which encodes a membrane-associated antagonist of Notch signaling, is a likely target of Msi1...
  14. Zhou P, Alfaro J, Chang E, Zhao X, Porcionatto M, Segal R. Numb links extracellular cues to intracellular polarity machinery to promote chemotaxis. Dev Cell. 2011;20:610-22 pubmed publisher
    ..Here, we show that the endocytic adaptor protein Numb, previously characterized for its role in cell proliferation, subsequently plays an important role in cell ..
  15. Dho S, French M, Woods S, McGlade C. Characterization of four mammalian numb protein isoforms. Identification of cytoplasmic and membrane-associated variants of the phosphotyrosine binding domain. J Biol Chem. 1999;274:33097-104 pubmed
    b>Numb is a membrane-associated, phosphotyrosine binding (PTB) domain-containing protein that functions as an intrinsic determinant of cell fate during Drosophila development...
  16. Zhong W, Feder J, Jiang M, Jan L, Jan Y. Asymmetric localization of a mammalian numb homolog during mouse cortical neurogenesis. Neuron. 1996;17:43-53 pubmed
    During Drosophila neurogenesis, differential segregation of Numb is necessary for daughter cells of asymmetric divisions to adopt distinct fates, at least partly by biasing the Notch-mediated cell-cell interaction...
  17. Yokota Y, Kim W, Chen Y, Wang X, Stanco A, Komuro Y, et al. The adenomatous polyposis coli protein is an essential regulator of radial glial polarity and construction of the cerebral cortex. Neuron. 2009;61:42-56 pubmed publisher
    ..Thus, APC is an essential regulator of radial glial polarity and is critical for the construction of cerebral cortex in mammals. ..
  18. Rasin M, Gazula V, Breunig J, Kwan K, Johnson M, Liu Chen S, et al. Numb and Numbl are required for maintenance of cadherin-based adhesion and polarity of neural progenitors. Nat Neurosci. 2007;10:819-27 pubmed
    ..Here, we show that mouse numb and numb-like are required for maintaining radial glial adherens junctions...
  19. Jory A, Le Roux I, Gayraud Morel B, Rocheteau P, Cohen Tannoudji M, Cumano A, et al. Numb promotes an increase in skeletal muscle progenitor cells in the embryonic somite. Stem Cells. 2009;27:2769-80 pubmed publisher
    ..The asymmetric cell fate determinant Numb is thought to promote differentiation of skeletal muscle and other lineages by negatively regulating Notch ..
  20. Petersen P, Tang H, Zou K, Zhong W. The enigma of the numb-Notch relationship during mammalian embryogenesis. Dev Neurosci. 2006;28:156-68 pubmed
    ..In Drosophila, two signaling pathways, one mediated by Numb and the other by Notch, play essential but antagonistic roles in enabling the two daughters to adopt different ..
  21. Zhong W, Jiang M, Schonemann M, Meneses J, Pedersen R, Jan L, et al. Mouse numb is an essential gene involved in cortical neurogenesis. Proc Natl Acad Sci U S A. 2000;97:6844-9 pubmed
    ..The mouse numb (m-numb) gene encodes a membrane-associated protein that is asymmetrically localized to the apical cell membrane of ..
  22. El Hashash A, Turcatel G, Al Alam D, Buckley S, Tokumitsu H, Bellusci S, et al. Eya1 controls cell polarity, spindle orientation, cell fate and Notch signaling in distal embryonic lung epithelium. Development. 2011;138:1395-407 pubmed publisher
    ..these findings, spindle orientation-regulatory proteins Insc, LGN (Gpsm2) and NuMA, and the cell fate determinant Numb are asymmetrically localized in embryonic lung distal epithelium...
  23. Yu C, Rafiq N, Cao F, Zhou Y, Krishnasamy A, Biswas K, et al. Integrin-beta3 clusters recruit clathrin-mediated endocytic machinery in the absence of traction force. Nat Commun. 2015;6:8672 pubmed publisher
    ..From these observations, we propose that loss of traction force on ligand-bound integrin-beta3 causes recruitment of Dab2/clathrin, resulting in endocytosis of integrins. ..
  24. Nie J, Li S, McGlade C. A novel PTB-PDZ domain interaction mediates isoform-specific ubiquitylation of mammalian Numb. J Biol Chem. 2004;279:20807-15 pubmed
    LNX was originally cloned as a Numb PTB-binding molecule, and it was subsequently found to act as a RING finger-type E3 ubiquitin ligase for the ubiquitylation and degradation of mNumb...
  25. Klein A, Zilian O, Suter U, Taylor V. Murine numb regulates granule cell maturation in the cerebellum. Dev Biol. 2004;266:161-77 pubmed
    Notch is a key regulator of vertebrate neurogenesis and the cytoplasmic adaptor protein Numb is a modulator of the Notch signaling pathway...
  26. Kim K, Nam J, Mukouyama Y, Kawamoto S. Rbfox3-regulated alternative splicing of Numb promotes neuronal differentiation during development. J Cell Biol. 2013;200:443-58 pubmed publisher
    ..b>Numb premRNA encoding a signaling adaptor protein was found to be a target of Rbfox3 action, and Rbfox3 repressed the ..
  27. Carson C, Murdoch B, Roskams A. Notch 2 and Notch 1/3 segregate to neuronal and glial lineages of the developing olfactory epithelium. Dev Dyn. 2006;235:1678-88 pubmed
    ..Notch 2 and Notch 1/3 may, therefore, have different roles in the commitment and differentiation of neuronal and glial lineages of the OE during development, and the maintenance of non-neuronal phenotypes postnatally. ..
  28. Li H, Wang D, Shen Q, Schonemann M, Gorski J, Jones K, et al. Inactivation of Numb and Numblike in embryonic dorsal forebrain impairs neurogenesis and disrupts cortical morphogenesis. Neuron. 2003;40:1105-18 pubmed
    b>Numb and Numblike, conserved homologs of Drosophila Numb, have been implicated in cortical neurogenesis; however, analysis of their involvement in later stages of cortical development has been hampered by early lethality of double mutants ..
  29. Jiang X, Xing H, Kim T, Jung Y, Huang W, Yang H, et al. Numb regulates glioma stem cell fate and growth by altering epidermal growth factor receptor and Skp1-Cullin-F-box ubiquitin ligase activity. Stem Cells. 2012;30:1313-26 pubmed publisher
    ..Here, we show that asymmetric Numb localization specifies glioblastoma stem-like cell (GSC) fate in a manner that does not require Notch inhibition...
  30. Ting S, Deneault E, Hope K, Cellot S, Chagraoui J, Mayotte N, et al. Asymmetric segregation and self-renewal of hematopoietic stem and progenitor cells with endocytic Ap2a2. Blood. 2012;119:2510-22 pubmed publisher
    ..These results contribute further evidence that ACD is functional in HSC self-renewal, suggest a role for Ap2a2 in HSC activity, and provide a unique opportunity to prospectively analyze progeny from HSC asymmetric divisions. ..
  31. Zilian O, Saner C, Hagedorn L, Lee H, Sauberli E, Suter U, et al. Multiple roles of mouse Numb in tuning developmental cell fates. Curr Biol. 2001;11:494-501 pubmed
    ..b>Numb encodes an intracellular protein that was shown in Drosophila to antagonize Notch signaling at binary cell fate ..
  32. Wu M, Smith C, Hall J, Lee I, Luby Phelps K, Tallquist M. Epicardial spindle orientation controls cell entry into the myocardium. Dev Cell. 2010;19:114-25 pubmed publisher
    ..Loss of adherens junctions also disrupted Numb localization within epicardial cells, and disruption of Numb and Numblike expression in the epicardium led to ..
  33. El Hashash A, Warburton D. Cell polarity and spindle orientation in the distal epithelium of embryonic lung. Dev Dyn. 2011;240:441-5 pubmed publisher
    ..Furthermore, the cell fate determinant Numb is asymmetrically distributed at the apical side of distal epithelial progenitors and segregated to one daughter ..
  34. Aguirre A, Rubio M, Gallo V. Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal. Nature. 2010;467:323-7 pubmed publisher
    ..Our findings define a novel interaction between EGFR and Notch pathways in the adult SVZ, and thus provide a mechanism for NSC and NPC pool maintenance...
  35. Krieger J, Taylor P, Gajadhar A, Guha A, Moran M, McGlade C. Identification and selected reaction monitoring (SRM) quantification of endocytosis factors associated with Numb. Mol Cell Proteomics. 2013;12:499-514 pubmed publisher
    b>Numb is an endocytic adaptor protein that regulates the endocytosis and trafficking of transmembrane receptors including Notch, E-cadherin, and integrins...
  36. Kennedy K, Ostrakhovitch E, Sandiford S, Dayarathna T, Xie X, Waese E, et al. Mammalian numb-interacting protein 1/dual oxidase maturation factor 1 directs neuronal fate in stem cells. J Biol Chem. 2010;285:17974-85 pubmed publisher
    In this study, we describe a role for the mammalian Numb-interacting protein 1 (Nip1) in regulation of neuronal differentiation in stem cells...
  37. Hirai M, Arita Y, McGlade C, Lee K, Chen J, Evans S. Adaptor proteins NUMB and NUMBL promote cell cycle withdrawal by targeting ERBB2 for degradation. J Clin Invest. 2017;127:569-582 pubmed publisher
    ..Here, we have found that the endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2 signaling in maturing trabeculae...
  38. Grisanti L, Corallini S, Fera S, Muciaccia B, Stefanini M, Witke W, et al. Inactivation of Numb and Numblike in spermatogonial stem cells by cell-permeant Cre recombinase. Differentiation. 2009;78:131-6 pubmed publisher
    ..The adaptor protein Numb is an evolutionarily conserved protein originally implicated in the control of the fate of sibling cells...
  39. Tarn W, Kuo H, Yu H, Liu S, Tseng C, Dhananjaya D, et al. RBM4 promotes neuronal differentiation and neurite outgrowth by modulating Numb isoform expression. Mol Biol Cell. 2016;27:1676-83 pubmed publisher
    ..model, we observed a temporal correlation between RBM4 expression and a change in splicing isoforms of Numb, a cell-fate determination gene...
  40. Shao X, Ding Z, Zhao M, Liu K, Sun H, Chen J, et al. Mammalian Numb protein antagonizes Notch by controlling postendocytic trafficking of the Notch ligand Delta-like 4. J Biol Chem. 2017;: pubmed publisher
    The biological antagonism between the signaling proteins Numb and Notch has been implicated in the regulation of many developmental processes, especially in asymmetric cell division...
  41. Cheng X, Huber T, Chen V, Gadue P, Keller G. Numb mediates the interaction between Wnt and Notch to modulate primitive erythropoietic specification from the hemangioblast. Development. 2008;135:3447-58 pubmed publisher
    ..Inhibition of Notch signaling at this stage appears to be mediated by the transient expression of Numb in the hemangioblast-derived blast cell colonies...
  42. Ramamurthy V, Jolicoeur C, Koutroumbas D, Mühlhans J, Le Y, Hauswirth W, et al. Numb regulates the polarized delivery of cyclic nucleotide-gated ion channels in rod photoreceptor cilia. J Neurosci. 2014;34:13976-87 pubmed publisher
    ..We report here that the endocytic adaptor protein Numb localizes to the inner, but not the outer segment of mouse photoreceptor cilia...
  43. Yang J, Hung L, Licht T, Kostin S, Looso M, Khrameeva E, et al. RBM24 is a major regulator of muscle-specific alternative splicing. Dev Cell. 2014;31:87-99 pubmed publisher
    ..Introduction of ESS and ISE converted a constitutive exon into an RMB24-dependent alternative exon. We reason that RBM24 is a major regulator of alternative splicing in striated muscles...
  44. Klezovitch O, Fernandez T, Tapscott S, Vasioukhin V. Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice. Genes Dev. 2004;18:559-71 pubmed
    ..Dividing Lgl1(-/-) cells are unable to asymmetrically localize the Notch inhibitor Numb, and the resulting failure of asymmetric cell divisions may be responsible for the hyperproliferation and the lack ..