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. McGill M, Dho S, Weinmaster G, McGlade C. Numb regulates post-endocytic trafficking and degradation of Notch1. J Biol Chem. 2009;284:26427-38 pubmed publisher
    ..Both activation and attenuation of the Notch signal are tightly regulated by endocytosis. The adaptor protein Numb acts as an inhibitor of Notch and is known to function within the intracellular trafficking pathways...
  3. 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 ..
  4. Dho S, Trejo J, Siderovski D, McGlade C. Dynamic regulation of mammalian numb by G protein-coupled receptors and protein kinase C activation: Structural determinants of numb association with the cortical membrane. Mol Biol Cell. 2006;17:4142-55 pubmed
    The cell fate determinant Numb is a membrane-associated adaptor protein involved in both development and intracellular vesicular trafficking...
  5. 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...
  6. 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 ..
  7. Bani Yaghoub M, Kubu C, Cowling R, Rochira J, Nikopoulos G, Bellum S, et al. A switch in numb isoforms is a critical step in cortical development. Dev Dyn. 2007;236:696-705 pubmed
    Loss of numb function suggests that numb maintains progenitors in an undifferentiated state...
  8. 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...
  9. Aguado R, Martin Blanco N, Caraballo M, Canelles M. The endocytic adaptor Numb regulates thymus size by modulating pre-TCR signaling during asymmetric division. Blood. 2010;116:1705-14 pubmed publisher
    ..Several cell fate determinants participate in asymmetric division, with the endocytic adaptor Numb as the best-known example...
  10. 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...

Detail Information

Publications81

  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. McGill M, Dho S, Weinmaster G, McGlade C. Numb regulates post-endocytic trafficking and degradation of Notch1. J Biol Chem. 2009;284:26427-38 pubmed publisher
    ..Both activation and attenuation of the Notch signal are tightly regulated by endocytosis. The adaptor protein Numb acts as an inhibitor of Notch and is known to function within the intracellular trafficking pathways...
  3. 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 ..
  4. Dho S, Trejo J, Siderovski D, McGlade C. Dynamic regulation of mammalian numb by G protein-coupled receptors and protein kinase C activation: Structural determinants of numb association with the cortical membrane. Mol Biol Cell. 2006;17:4142-55 pubmed
    The cell fate determinant Numb is a membrane-associated adaptor protein involved in both development and intracellular vesicular trafficking...
  5. 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...
  6. 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 ..
  7. Bani Yaghoub M, Kubu C, Cowling R, Rochira J, Nikopoulos G, Bellum S, et al. A switch in numb isoforms is a critical step in cortical development. Dev Dyn. 2007;236:696-705 pubmed
    Loss of numb function suggests that numb maintains progenitors in an undifferentiated state...
  8. 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...
  9. Aguado R, Martin Blanco N, Caraballo M, Canelles M. The endocytic adaptor Numb regulates thymus size by modulating pre-TCR signaling during asymmetric division. Blood. 2010;116:1705-14 pubmed publisher
    ..Several cell fate determinants participate in asymmetric division, with the endocytic adaptor Numb as the best-known example...
  10. 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...
  11. 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...
  12. 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...
  13. 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...
  14. 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 ..
  15. 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...
  16. 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 ..
  17. 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...
  18. 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 ..
  19. 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...
  20. 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. ..
  21. 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...
  22. 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 ..
  23. 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...
  24. Gulino A, Di Marcotullio L, Screpanti I. The multiple functions of Numb. Exp Cell Res. 2010;316:900-6 pubmed publisher
    b>Numb is an evolutionary conserved protein that plays critical roles in cell fate determination...
  25. 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 ..
  26. 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 ..
  27. French M, Koch U, Shaye R, McGill M, Dho S, Guidos C, et al. Transgenic expression of numb inhibits notch signaling in immature thymocytes but does not alter T cell fate specification. J Immunol. 2002;168:3173-80 pubmed
    The conserved adaptor protein Numb is an intrinsic cell fate determinant that functions by antagonizing Notch-mediated signal transduction...
  28. Lacomme M, Tarchini B, Boudreau Pinsonneault C, Monat C, Cayouette M. The LGN protein promotes planar proliferative divisions in the neocortex but apicobasal asymmetric terminal divisions in the retina. Development. 2016;143:575-81 pubmed publisher
  29. Chan S, Pedersen W, Zhu H, Mattson M. Numb modifies neuronal vulnerability to amyloid beta-peptide in an isoform-specific manner by a mechanism involving altered calcium homeostasis: implications for neuronal death in Alzheimer's disease. Neuromolecular Med. 2002;1:55-67 pubmed
    ..The actions of Notch can be antagonized by Numb, an evolutionarily conserved protein that exists in four isoforms that differ in two functional domains: a ..
  30. Liu L, Lanner F, Lendahl U, Das D. Numblike and Numb differentially affect p53 and Sonic Hedgehog signaling. Biochem Biophys Res Commun. 2011;413:426-31 pubmed publisher
    b>Numb serves as a key regulator of Notch and Sonic Hedgehog signaling and also modulates p53 protein levels. Numblike is a highly conserved homolog to mammalian Numb, but considerably less is known about its function...
  31. Roncarati R, Sestan N, Scheinfeld M, Berechid B, Lopez P, Meucci O, et al. The gamma-secretase-generated intracellular domain of beta-amyloid precursor protein binds Numb and inhibits Notch signaling. Proc Natl Acad Sci U S A. 2002;99:7102-7 pubmed
    ..Here, we show that membrane-tethered APP binds to the cytosolic Notch inhibitors Numb and Numb-like in mouse brain lysates...
  32. Yoshida T, Tokunaga A, Nakao K, Okano H. Distinct expression patterns of splicing isoforms of mNumb in the endocrine lineage of developing pancreas. Differentiation. 2003;71:486-95 pubmed
    ..Mammalian Numb (mNumb) is an ortholog of Drosophila Numb (dNumb), which is likely to be an intracellular inhibitor of Notch ..
  33. Beres B, George R, Lougher E, Barton M, Verrelli B, McGlade C, et al. Numb regulates Notch1, but not Notch3, during myogenesis. Mech Dev. 2011;128:247-57 pubmed publisher
    ..The current data demonstrate that Notch3 also is an effective inhibitor of MyoD induced myogenesis. Numb, an adaptor protein that promotes Notch degradation by recruiting the E3 ubiquitin ligase, Itch, is limited in ..
  34. Takahashi T, Suzuki H, Imai T, Shibata S, Tabuchi Y, Tsuchimoto K, et al. Musashi-1 post-transcriptionally enhances phosphotyrosine-binding domain-containing m-Numb protein expression in regenerating gastric mucosa. PLoS ONE. 2013;8:e53540 pubmed publisher
    ..gastric mucosal injury with Msi1-knock-out (KO) mice to clarify the role of Msi1 and Msi1-dependent regulation of m-Numb expression in regenerating gastric mucosa...
  35. Raji B, Dansault A, Vieira V, de la Houssaye G, Lacassagne E, Kobetz A, et al. Analysis of partner of inscuteable (mPins) expression in the developing mouse eye. Mol Vis. 2008;14:2575-96 pubmed
    ..At these stages, mPins protein was colocalized with Numb protein, a marker of the ACD...
  36. Hayashi T, Lombaert I, Hauser B, Patel V, Hoffman M. Exosomal MicroRNA Transport from Salivary Mesenchyme Regulates Epithelial Progenitor Expansion during Organogenesis. Dev Cell. 2017;40:95-103 pubmed publisher
    ..In summary, exosomal transport of miR-133b-3p from mesenchyme to epithelium decreases DIP2B, which may function as an epigenetic regulator of genes responsible for KIT+ progenitor expansion during organogenesis. ..
  37. Theil T. Gli3 is required for the specification and differentiation of preplate neurons. Dev Biol. 2005;286:559-71 pubmed
  38. Martin Blanco N, Jiménez Teja D, Bretones G, Borroto A, Caraballo M, Screpanti I, et al. CD3ε recruits Numb to promote TCR degradation. Int Immunol. 2016;28:127-37 pubmed publisher
    ..Here, we describe the role of a new player in the mediation of TCR degradation: the endocytic adaptor Numb. Our data show that Numb inhibition leads to abnormal intracellular distribution and defective TCR degradation in ..
  39. Li P, Fu Z, Zhang Y, Zhang J, Xu C, Ma Y, et al. The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1. Nat Med. 2014;20:80-6 pubmed publisher
    ..of NPC1L1 released the YVNXXF-containing region of NPC1L1 from association with the plasma membrane and enabled Numb binding...
  40. Nie J, McGill M, Dermer M, Dho S, Wolting C, McGlade C. LNX functions as a RING type E3 ubiquitin ligase that targets the cell fate determinant Numb for ubiquitin-dependent degradation. EMBO J. 2002;21:93-102 pubmed
    LNX is a RING finger and PDZ domain containing protein that interacts with the cell fate determinant Numb. To investigate the function of LNX, we tested its RING finger domain for ubiquitin ligase activity...
  41. Smith C, Dho S, Donaldson J, Tepass U, McGlade C. The cell fate determinant numb interacts with EHD/Rme-1 family proteins and has a role in endocytic recycling. Mol Biol Cell. 2004;15:3698-708 pubmed
    The adaptor protein Numb is necessary for the cell fate specification of progenitor cells in the Drosophila nervous system...
  42. Moore R, Cai K, Tao W, Smith E, Xu X. Differential requirement for Dab2 in the development of embryonic and extra-embryonic tissues. BMC Dev Biol. 2013;13:39 pubmed publisher
    ..Experimental results with embryoid bodies suggest that additional endocytic adaptors such as Arh and Numb could partially compensate for Dab2 loss...
  43. Di Marcotullio L, Ferretti E, Greco A, De Smaele E, Po A, Sico M, et al. Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination. Nat Cell Biol. 2006;8:1415-23 pubmed
    The developmental protein Numb is a major determinant of binary cell fates...
  44. George R, Biressi S, Beres B, Rogers E, Mulia A, Allen R, et al. Numb-deficient satellite cells have regeneration and proliferation defects. Proc Natl Acad Sci U S A. 2013;110:18549-54 pubmed publisher
    The adaptor protein Numb has been implicated in the switch between cell proliferation and differentiation made by satellite cells during muscle repair...
  45. Chigurupati S, Madan M, Okun E, Wei Z, Pattisapu J, Mughal M, et al. Evidence for altered Numb isoform levels in Alzheimer's disease patients and a triple transgenic mouse model. J Alzheimers Dis. 2011;24:349-61 pubmed publisher
    The cell fate determinant Numb exists in four alternatively spliced variants that differ in the length of their PTB (phosphotyrosine-binding domain, either lacking or containing an 11 amino acid insertion) and PRR (proline-rich region, ..
  46. Zhao C, Guo H, Li J, Myint T, Pittman W, Yang L, et al. Numb family proteins are essential for cardiac morphogenesis and progenitor differentiation. Development. 2014;141:281-95 pubmed publisher
    b>Numb family proteins (NFPs), including Numb and numb-like (Numbl), are cell fate determinants for multiple progenitor cell types. Their functions in cardiac progenitor differentiation and cardiac morphogenesis are unknown...
  47. Zhou L, Yang D, Wang D, Xie Y, Zhou J, Zhou L, et al. Numb deficiency in cerebellar Purkinje cells impairs synaptic expression of metabotropic glutamate receptor and motor coordination. Proc Natl Acad Sci U S A. 2015;112:15474-9 pubmed publisher
    Protein Numb, first identified as a cell-fate determinant in Drosophila, has been shown to promote the development of neurites in mammals and to be cotransported with endocytic receptors in clathrin-coated vesicles in vitro...
  48. 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 ..
  49. 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. ..
  50. 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. ..
  51. Gulino R, Parenti R, Gulisano M. Novel Mechanisms of Spinal Cord Plasticity in a Mouse Model of Motoneuron Disease. Biomed Res Int. 2015;2015:654637 pubmed publisher
    ..We have previously studied some mechanisms of spinal plasticity involving BDNF, Shh, Notch-1, Numb, and Noggin, by using a mouse model of motoneuron depletion induced by cholera toxin-B saporin...
  52. Fassa A, Mehta P, Efthimiopoulos S. Notch 1 interacts with the amyloid precursor protein in a Numb-independent manner. J Neurosci Res. 2005;82:214-24 pubmed
    ..The APP(751)/mN1 interaction was Numb-independent, insofar as it was observed in HEK293 cells that lack detectable levels of Numb and was unaffected by ..
  53. 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...
  54. 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...
  55. 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 ..
  56. 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. ..
  57. Huang E, Li H, Tang A, Wiggins A, Neve R, Zhong W, et al. Targeted deletion of numb and numblike in sensory neurons reveals their essential functions in axon arborization. Genes Dev. 2005;19:138-51 pubmed
    Mouse Numb homologs antagonize Notch1 signaling pathways through largely unknown mechanisms...
  58. Shenje L, Andersen P, Uosaki H, Fernandez L, Rainer P, Cho G, et al. Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors. elife. 2014;3:e02164 pubmed publisher
    ..Here, we show that deletion of the ancient cell-fate regulator Numb (Nb) and its homologue Numblike (Nbl) depletes CPCs in second pharyngeal arches (PA2s) and is associated with an ..
  59. 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 ..
  60. 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 ..
  61. 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 ..
  62. 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...
  63. 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...
  64. 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...
  65. 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...
  66. Feldman D, Chen C, Punj V, Machida K. The TBC1D15 oncoprotein controls stem cell self-renewal through destabilization of the Numb-p53 complex. PLoS ONE. 2013;8:e57312 pubmed publisher
    ..The p53 tumor suppressor, in conjunction with its interacting partner protein Numb, preserves this asymmetry and functions as a vital barrier against the unchecked expansion of tumor stem cell pools;..
  67. 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...
  68. 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...
  69. Swarnkar G, Karuppaiah K, Mbalaviele G, Chen T, Abu Amer Y. Osteopetrosis in TAK1-deficient mice owing to defective NF-?B and NOTCH signaling. Proc Natl Acad Sci U S A. 2015;112:154-9 pubmed publisher
    ..Mechanistically, Tak1 deficiency correlated with increased NUMB-like (NUMBL) levels...
  70. 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...
  71. Tiberi L, van den Ameele J, Dimidschstein J, Piccirilli J, Gall D, Herpoel A, et al. BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets. Nat Neurosci. 2012;15:1627-35 pubmed publisher
    ..Our findings suggest a role for BCL6 in neurogenesis and uncover Notch-BCL6-Sirt1 interactions that may affect other aspects of physiology and disease. ..
  72. 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;292:20628-20643 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...
  73. Bu P, Wang L, Chen K, Srinivasan T, Murthy P, Tung K, et al. A miR-34a-Numb Feedforward Loop Triggered by Inflammation Regulates Asymmetric Stem Cell Division in Intestine and Colon Cancer. Cell Stem Cell. 2016;18:189-202 pubmed publisher
    ..Here, we show that miR-34a directly suppresses Numb in early-stage colon cancer stem cells (CCSCs), forming an incoherent feedforward loop (IFFL) targeting Notch to ..
  74. 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 ..
  75. Schnatwinkel C, Niswander L. Nubp1 is required for lung branching morphogenesis and distal progenitor cell survival in mice. PLoS ONE. 2012;7:e44871 pubmed publisher
    ..In addition, Nubp1 mutation disrupts localization of the polarity protein Par3 and the mitosis relevant protein Numb. Using knock-down studies in lung epithelial cells, we also demonstrate a function of Nubp1 in regulating ..
  76. Kueanjinda P, Roytrakul S, Palaga T. A Novel Role of Numb as A Regulator of Pro-inflammatory Cytokine Production in Macrophages in Response to Toll-like Receptor 4. Sci Rep. 2015;5:12784 pubmed publisher
    Activation of macrophages triggers the release of pro-inflammatory cytokines leading to inflammation. Numb is a negative regulator of Notch signaling, but the role of Numb in macrophages is not fully understood...
  77. 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...
  78. 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...
  79. 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...